HAEM5:B-lymphoblastic leukaemia/lymphoma with BCR::ABL1-like features: Difference between revisions

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{{DISPLAYTITLE:B-lymphoblastic leukaemia/lymphoma with BCR::ABL1-like features}}
{{DISPLAYTITLE:B-lymphoblastic leukaemia/lymphoma with ''BCR::ABL1''-like features}}
 
[[HAEM5:Table_of_Contents|Haematolymphoid Tumours (WHO Classification, 5th ed.)]]
[[HAEM5:Table_of_Contents|Haematolymphoid Tumours (WHO Classification, 5th ed.)]]


{{Under Construction}}
{{Under Construction}}


<blockquote class='blockedit'>{{Box-round|title=Content Update To WHO 5th Edition Classification Is In Process; Content Below is Based on WHO 4th Edition Classification|This page was converted to the new template on 2023-12-07. The original page can be found at [[HAEM4:B-Lymphoblastic Leukemia/Lymphoma, BCR-ABL1-Like]].
<blockquote class="blockedit">{{Box-round|title=Content Update To WHO 5th Edition Classification Is In Process; Content Below is Based on WHO 4th Edition Classification|This page was converted to the new template on 2023-12-07. The original page can be found at [[HAEM4:B-Lymphoblastic Leukemia/Lymphoma, BCR-ABL1-Like]].
}}</blockquote>
}}</blockquote>


<span style="color:#0070C0">(General Instructions – The main focus of these pages is the clinically significant genetic alterations in each disease type. Use [https://www.genenames.org/ <u>HUGO-approved gene names and symbols</u>] (italicized when appropriate), [https://varnomen.hgvs.org/ HGVS-based nomenclature for variants], as well as generic names of drugs and testing platforms or assays if applicable. Please complete tables whenever possible and do not delete them (add N/A if not applicable in the table and delete the examples); to add (or move) a row or column to a table, click within the table and select the > symbol that appears to be given options. Please do not delete or alter the section headings. The use of bullet points alongside short blocks of text rather than only large paragraphs is encouraged. Additional instructions below in italicized blue text should not be included in the final page content. Please also see </span><u>[[Author_Instructions]]</u><span style="color:#0070C0"> and [[Frequently Asked Questions (FAQs)|<u>FAQs</u>]] as well as contact your [[Leadership|<u>Associate Editor</u>]] or [mailto:CCGA@cancergenomics.org <u>Technical Support</u>])</span>
<span style="color:#0070C0">(General Instructions – The focus of these pages is the clinically significant genetic alterations in each disease type. This is based on up-to-date knowledge from multiple resources such as PubMed and the WHO classification books. The CCGA is meant to be a supplemental resource to the WHO classification books; the CCGA captures in a continually updated wiki-stye manner the current genetics/genomics knowledge of each disease, which evolves more rapidly than books can be revised and published. If the same disease is described in multiple WHO classification books, the genetics-related information for that disease will be consolidated into a single main page that has this template (other pages would only contain a link to this main page). Use [https://www.genenames.org/ <u>HUGO-approved gene names and symbols</u>] (italicized when appropriate), [https://varnomen.hgvs.org/ <u>HGVS-based nomenclature for variants</u>], as well as generic names of drugs and testing platforms or assays if applicable. Please complete tables whenever possible and do not delete them (add N/A if not applicable in the table and delete the examples); to add (or move) a row or column in a table, click nearby within the table and select the > symbol that appears. Please do not delete or alter the section headings. The use of bullet points alongside short blocks of text rather than only large paragraphs is encouraged. Additional instructions below in italicized blue text should not be included in the final page content. Please also see </span><u>[[Author_Instructions]]</u><span style="color:#0070C0"> and [[Frequently Asked Questions (FAQs)|<u>FAQs</u>]] as well as contact your [[Leadership|<u>Associate Editor</u>]] or [mailto:CCGA@cancergenomics.org <u>Technical Support</u>].)</span>


==Primary Author(s)*==
==Primary Author(s)*==
Mark G. Evans, MD, University of California, Irvine
Mark G. Evans, MD, Caris Life Sciences
 
Fabiola Quintero-Rivera, MD, University of California, Irvine
 
__TOC__


Sumire K. Kitahara, MD, Cedars-Sinai Medical Center
==WHO Classification of Disease==
==WHO Classification of Disease==


Line 35: Line 33:
|-
|-
|Subtype(s)
|Subtype(s)
|B-lymphoblastic leukaemia/lymphoma with BCR::ABL1-like features
|B-lymphoblastic leukaemia/lymphoma with ''BCR::ABL1''-like features
|}
|}


==Definition / Description of Disease==
==Related Terminology==
In 2009, a high-risk subgroup of B-ALL was identified in children, adolescents, and young adults<ref name=":0">{{Cite journal|last=Den Boer|first=Monique L.|last2=van Slegtenhorst|first2=Marjon|last3=De Menezes|first3=Renée X.|last4=Cheok|first4=Meyling H.|last5=Buijs-Gladdines|first5=Jessica G. C. A. M.|last6=Peters|first6=Susan T. C. J. M.|last7=Van Zutven|first7=Laura J. C. M.|last8=Beverloo|first8=H. Berna|last9=Van der Spek|first9=Peter J.|date=2009|title=A subtype of childhood acute lymphoblastic leukaemia with poor treatment outcome: a genome-wide classification study|url=https://www.ncbi.nlm.nih.gov/pubmed/19138562|journal=The Lancet. Oncology|volume=10|issue=2|pages=125–134|doi=10.1016/S1470-2045(08)70339-5|issn=1474-5488|pmc=2707020|pmid=19138562}}</ref><ref name=":1">{{Cite journal|last=Mullighan|first=Charles G.|last2=Su|first2=Xiaoping|last3=Zhang|first3=Jinghui|last4=Radtke|first4=Ina|last5=Phillips|first5=Letha A. A.|last6=Miller|first6=Christopher B.|last7=Ma|first7=Jing|last8=Liu|first8=Wei|last9=Cheng|first9=Cheng|date=2009|title=Deletion of IKZF1 and prognosis in acute lymphoblastic leukemia|url=https://www.ncbi.nlm.nih.gov/pubmed/19129520|journal=The New England Journal of Medicine|volume=360|issue=5|pages=470–480|doi=10.1056/NEJMoa0808253|issn=1533-4406|pmc=2674612|pmid=19129520}}</ref><ref>{{Cite journal|last=Roberts|first=Kathryn G.|last2=Morin|first2=Ryan D.|last3=Zhang|first3=Jinghui|last4=Hirst|first4=Martin|last5=Zhao|first5=Yongjun|last6=Su|first6=Xiaoping|last7=Chen|first7=Shann-Ching|last8=Payne-Turner|first8=Debbie|last9=Churchman|first9=Michelle L.|date=2012|title=Genetic alterations activating kinase and cytokine receptor signaling in high-risk acute lymphoblastic leukemia|url=https://www.ncbi.nlm.nih.gov/pubmed/22897847|journal=Cancer Cell|volume=22|issue=2|pages=153–166|doi=10.1016/j.ccr.2012.06.005|issn=1878-3686|pmc=3422513|pmid=22897847}}</ref>. The genetic expression is similar to that of BCR-ABL1-positive cases, but without t(9;22)(q34.1;q11.2). Instead, BCR-ABL-1-like B-ALL is a genetically heterogenous disease, often with alterations activating cytokine receptors and tyrosine kinases. Several genetic expression profiles were initially utilized to recognize cases<ref name=":0" /><ref name=":1" />, however, different profiles did not always identify the same patients<ref name=":3">{{Cite journal|last=Boer|first=Judith M.|last2=Marchante|first2=João R. M.|last3=Evans|first3=William E.|last4=Horstmann|first4=Martin A.|last5=Escherich|first5=Gabriele|last6=Pieters|first6=Rob|last7=Den Boer|first7=Monique L.|date=2015|title=BCR-ABL1-like cases in pediatric acute lymphoblastic leukemia: a comparison between DCOG/Erasmus MC and COG/St. Jude signatures|url=https://www.ncbi.nlm.nih.gov/pubmed/26045294|journal=Haematologica|volume=100|issue=9|pages=e354–357|doi=10.3324/haematol.2015.124941|issn=1592-8721|pmc=4800707|pmid=26045294}}</ref>. Although emerging data advocates the therapeutic use of tyrosine kinase or JAK inhibitors in this disease process, BCR-ABL-like B-ALL is often associated with very high rates of relapse and poor overall survival; thus proper diagnosis is essential<ref>{{Cite journal|last=Roberts|first=Kathryn G.|last2=Reshmi|first2=Shalini C.|last3=Harvey|first3=Richard C.|last4=Chen|first4=I.-Ming|last5=Patel|first5=Kinnari|last6=Stonerock|first6=Eileen|last7=Jenkins|first7=Heather|last8=Dai|first8=Yunfeng|last9=Valentine|first9=Marc|date=2018|title=Genomic and outcome analyses of Ph-like ALL in NCI standard-risk patients: a report from the Children's Oncology Group|url=https://www.ncbi.nlm.nih.gov/pubmed/29997224|journal=Blood|volume=132|issue=8|pages=815–824|doi=10.1182/blood-2018-04-841676|issn=1528-0020|pmc=6107876|pmid=29997224}}</ref>.   
 
==Synonyms / Terminology==
Ph-like B-lymphoblastic leukemia/lymphoma


==Epidemiology / Prevalence==
*Ph-like ALL comprises up to 15% of childhood B-ALL, and 20 to 25% in adolescents and young adults<ref name=":4">{{Cite journal|last=Roberts|first=Kathryn G.|last2=Li|first2=Yongjin|last3=Payne-Turner|first3=Debbie|last4=Harvey|first4=Richard C.|last5=Yang|first5=Yung-Li|last6=Pei|first6=Deqing|last7=McCastlain|first7=Kelly|last8=Ding|first8=Li|last9=Lu|first9=Charles|date=2014|title=Targetable kinase-activating lesions in Ph-like acute lymphoblastic leukemia|url=https://www.ncbi.nlm.nih.gov/pubmed/25207766|journal=The New England Journal of Medicine|volume=371|issue=11|pages=1005–1015|doi=10.1056/NEJMoa1403088|issn=1533-4406|pmc=4191900|pmid=25207766}}</ref>.
*The incidence in adult patients is controversial—from 13-17% to up to 33% in some reports<ref>{{Cite journal|last=Boer|first=Judith M.|last2=Koenders|first2=Jasper E.|last3=van der Holt|first3=Bronno|last4=Exalto|first4=Carla|last5=Sanders|first5=Mathijs A.|last6=Cornelissen|first6=Jan J.|last7=Valk|first7=Peter J. M.|last8=den Boer|first8=Monique L.|last9=Rijneveld|first9=Anita W.|date=2015|title=Expression profiling of adult acute lymphoblastic leukemia identifies a BCR-ABL1-like subgroup characterized by high non-response and relapse rates|url=https://www.ncbi.nlm.nih.gov/pubmed/25769542|journal=Haematologica|volume=100|issue=7|pages=e261–264|doi=10.3324/haematol.2014.117424|issn=1592-8721|pmc=4486237|pmid=25769542}}</ref><ref name=":5">{{Cite journal|last=Herold|first=Tobias|last2=Schneider|first2=Stephanie|last3=Metzeler|first3=Klaus H.|last4=Neumann|first4=Martin|last5=Hartmann|first5=Luise|last6=Roberts|first6=Kathryn G.|last7=Konstandin|first7=Nikola P.|last8=Greif|first8=Philipp A.|last9=Bräundl|first9=Kathrin|date=2017|title=Adults with Philadelphia chromosome-like acute lymphoblastic leukemia frequently have IGH-CRLF2 and JAK2 mutations, persistence of minimal residual disease and poor prognosis|url=https://www.ncbi.nlm.nih.gov/pubmed/27561722|journal=Haematologica|volume=102|issue=1|pages=130–138|doi=10.3324/haematol.2015.136366|issn=1592-8721|pmc=5210243|pmid=27561722}}</ref><ref name=":6">{{Cite journal|last=Jain|first=Nitin|last2=Roberts|first2=Kathryn G.|last3=Jabbour|first3=Elias|last4=Patel|first4=Keyur|last5=Eterovic|first5=Agda Karina|last6=Chen|first6=Ken|last7=Zweidler-McKay|first7=Patrick|last8=Lu|first8=Xinyan|last9=Fawcett|first9=Gloria|date=2017|title=Ph-like acute lymphoblastic leukemia: a high-risk subtype in adults|url=https://www.ncbi.nlm.nih.gov/pubmed/27919910|journal=Blood|volume=129|issue=5|pages=572–581|doi=10.1182/blood-2016-07-726588|issn=1528-0020|pmc=5290985|pmid=27919910}}</ref>.
*Higher rates of disease are observed in Hispanic and Native-American populations, and among children with Down syndrome<ref>{{Cite journal|last=Harvey|first=Richard C.|last2=Mullighan|first2=Charles G.|last3=Chen|first3=I.-Ming|last4=Wharton|first4=Walker|last5=Mikhail|first5=Fady M.|last6=Carroll|first6=Andrew J.|last7=Kang|first7=Huining|last8=Liu|first8=Wei|last9=Dobbin|first9=Kevin K.|date=2010|title=Rearrangement of CRLF2 is associated with mutation of JAK kinases, alteration of IKZF1, Hispanic/Latino ethnicity, and a poor outcome in pediatric B-progenitor acute lymphoblastic leukemia|url=https://www.ncbi.nlm.nih.gov/pubmed/20139093|journal=Blood|volume=115|issue=26|pages=5312–5321|doi=10.1182/blood-2009-09-245944|issn=1528-0020|pmc=2902132|pmid=20139093}}</ref>.
==Clinical Features==
Put your text here and fill in the table <span style="color:#0070C0">(''Instruction: Can include references in the table. Do not delete table.'') </span>
{| class="wikitable"
{| class="wikitable"
|'''Signs and Symptoms'''
|+
|<span class="blue-text">EXAMPLE:</span> Asymptomatic (incidental finding on complete blood counts)
|Acceptable
 
|Philadelphia-like (Ph-like) B-ALL; ''BCR::ABL1''-like B-ALL/LBL
<span class="blue-text">EXAMPLE:</span> B-symptoms (weight loss, fever, night sweats)
 
<span class="blue-text">EXAMPLE:</span> Fatigue
 
<span class="blue-text">EXAMPLE:</span> Lymphadenopathy (uncommon)
|-
|-
|'''Laboratory Findings'''
|Not Recommended
|<span class="blue-text">EXAMPLE:</span> Cytopenias
|N/A
 
<span class="blue-text">EXAMPLE:</span> Lymphocytosis (low level)
|}
|}


==Gene Rearrangements==


<blockquote class='blockedit'>{{Box-round|title=v4:Clinical Features|The content below was from the old template. Please incorporate above.}}</blockquote>
B-lymphoblastic leukaemia/lymphoma with ''BCR::ABL1''-like features traditionally required diagnosis by gene expression (GEX) profiling<ref name=":1">{{Cite journal|last=Mullighan|first=Charles G.|last2=Su|first2=Xiaoping|last3=Zhang|first3=Jinghui|last4=Radtke|first4=Ina|last5=Phillips|first5=Letha A. A.|last6=Miller|first6=Christopher B.|last7=Ma|first7=Jing|last8=Liu|first8=Wei|last9=Cheng|first9=Cheng|date=2009|title=Deletion of IKZF1 and prognosis in acute lymphoblastic leukemia|url=https://www.ncbi.nlm.nih.gov/pubmed/19129520|journal=The New England Journal of Medicine|volume=360|issue=5|pages=470–480|doi=10.1056/NEJMoa0808253|issn=1533-4406|pmc=2674612|pmid=19129520}}</ref><ref name=":0">{{Cite journal|last=Den Boer|first=Monique L.|last2=van Slegtenhorst|first2=Marjon|last3=De Menezes|first3=Renée X.|last4=Cheok|first4=Meyling H.|last5=Buijs-Gladdines|first5=Jessica G. C. A. M.|last6=Peters|first6=Susan T. C. J. M.|last7=Van Zutven|first7=Laura J. C. M.|last8=Beverloo|first8=H. Berna|last9=Van der Spek|first9=Peter J.|date=2009|title=A subtype of childhood acute lymphoblastic leukaemia with poor treatment outcome: a genome-wide classification study|url=https://www.ncbi.nlm.nih.gov/pubmed/19138562|journal=The Lancet. Oncology|volume=10|issue=2|pages=125–134|doi=10.1016/S1470-2045(08)70339-5|issn=1474-5488|pmc=2707020|pmid=19138562}}</ref> and was found to exhibit a GEX profile similar to Philadelphia chromosome-positive B-lymphoblastic leukaemia/lymphoma but lacking ''BCR::ABL1''. The WHO<ref>WHO Classification of Tumours Editorial Board. Hematolymphoid tumors. Lyon (France): International Agency for Research on Cancer; 2022. [cited 2025 NOV 05]. (WHO classification of tumors series, 5th ed.). Available from: https:​//tumourclassification​.iarc.who.int.</ref> and ICC<ref>{{Cite journal|last=Campo|first=Elias|last2=Jaffe|first2=Elaine S.|last3=Cook|first3=James R.|last4=Quintanilla-Martinez|first4=Leticia|last5=Swerdlow|first5=Steven H.|last6=Anderson|first6=Kenneth C.|last7=Brousset|first7=Pierre|last8=Cerroni|first8=Lorenzo|last9=de Leval|first9=Laurence|date=2022-09-15|title=The International Consensus Classification of Mature Lymphoid Neoplasms: a report from the Clinical Advisory Committee|url=https://pubmed.ncbi.nlm.nih.gov/35653592|journal=Blood|volume=140|issue=11|pages=1229–1253|doi=10.1182/blood.2022015851|issn=1528-0020|pmc=9479027|pmid=35653592}}</ref> have since recognized recurring genomic alterations associated with B-lymphoblastic leukaemia/lymphoma with ''BCR::ABL1''-like features, including  ABL-class rearrangements, JAK-STAT activating alterations, and others. Proper identification of this disease is important, as patients may respond to targeted therapies like tyrosine kinase inhibitors (TKIs);<ref name=":9" /> however, as most reports feature only single cases and limited series, consensus on the diagnostic/prognostic/therapeutic significance of the various genomic alterations has not been reached and currently being established.
The presenting symptoms are similar to those of other ALL patients, with the exception of potentially higher white blood cell counts<ref name=":2">Borowitz MJ, et al., (2017). B-lymphoblastic leukaemia/lymphoma with recurrent genetic abnormalities, in World Health Organization Classification of Tumours of Haematopoietic and Lymphoid Tissues, Revised 4th edition. Swerdlow SH, Campo E, Harris NL, Jaffe ES, Pileri SA, Stein H, Thiele J, Arber DA, Hasserjian RP, Le Beau MM, Orazi A, and Siebert R, Editors. IARC Press: Lyon, France, p208.</ref>.


<blockquote class="blockedit">
<center><span style="color:Maroon">'''End of V4 Section'''</span>
----
</blockquote>
==Sites of Involvement==
Bone marrow


==Morphologic Features==
Table derived from Akkari et al., 2020 <ref>{{Cite journal|last=Akkari|first=Yassmine M. N.|last2=Bruyere|first2=Helene|last3=Hagelstrom|first3=R. Tanner|last4=Kanagal-Shamanna|first4=Rashmi|last5=Liu|first5=Jie|last6=Luo|first6=Minjie|last7=Mikhail|first7=Fady M.|last8=Pitel|first8=Beth A.|last9=Raca|first9=Gordana|date=2020-05|title=Evidence-based review of genomic aberrations in B-lymphoblastic leukemia/lymphoma: Report from the cancer genomics consortium working group for lymphoblastic leukemia|url=https://pubmed.ncbi.nlm.nih.gov/32302940|journal=Cancer Genetics|volume=243|pages=52–72|doi=10.1016/j.cancergen.2020.03.001|issn=2210-7762|pmid=32302940}}</ref> with permission from ''Cancer Genetics'' summarizes the important gene rearrangements associated with B-lymphoblastic leukaemia/lymphoma with ''BCR::ABL1''-like features.
There are no morphological or cytochemical features that aid in the diagnosis. Blasts range from small to large and chromatin varying from immature to more mature, corresponding to French-American-British classification L1 or L2 subtype<ref name=":7">{{Cite journal|last=Konoplev|first=Sergej|last2=Lu|first2=Xinyan|last3=Konopleva|first3=Marina|last4=Jain|first4=Nitin|last5=Ouyang|first5=Juan|last6=Goswami|first6=Maitrayee|last7=Roberts|first7=Kathryn G.|last8=Valentine|first8=Marc|last9=Mullighan|first9=Charles G.|date=2017|title=CRLF2-Positive B-Cell Acute Lymphoblastic Leukemia in Adult Patients: A Single-Institution Experience|url=https://www.ncbi.nlm.nih.gov/pubmed/28340183|journal=American Journal of Clinical Pathology|volume=147|issue=4|pages=357–363|doi=10.1093/ajcp/aqx005|issn=1943-7722|pmid=28340183}}</ref>.[[File:Morphologic Features.jpg|thumb|195x195px|(Konoplev et al. Am J Clin Pathol. 2017.)|link=http://www.ccga.io/index.php/File:Morphologic_Features.jpg|none]]
{| class="wikitable"
 
|'''3’ Partner'''
==Immunophenotype==
|'''5’ Partner'''
 
|'''Chromosome rearrangement'''
Put your text here and fill in the table <span style="color:#0070C0">(''Instruction: Can include references in the table. Do not delete table.'') </span>
|'''Gene fusion'''
 
|'''Visible by G-banding'''
{| class="wikitable sortable"
|'''References'''
|'''Comment'''
|-
| rowspan="12" |''[[ABL1]]''
(9q34)
|''CENPC1''
|t(4;9)(q13;q34)
|''CENPC1::ABL1''
|YES
|<ref name=":2">{{Cite journal|last=Reshmi|first=Shalini C.|last2=Harvey|first2=Richard C.|last3=Roberts|first3=Kathryn G.|last4=Stonerock|first4=Eileen|last5=Smith|first5=Amy|last6=Jenkins|first6=Heather|last7=Chen|first7=I.-Ming|last8=Valentine|first8=Marc|last9=Liu|first9=Yu|date=2017-06-22|title=Targetable kinase gene fusions in high-risk B-ALL: a study from the Children's Oncology Group|url=https://pubmed.ncbi.nlm.nih.gov/28408464|journal=Blood|volume=129|issue=25|pages=3352–3361|doi=10.1182/blood-2016-12-758979|issn=1528-0020|pmc=5482101|pmid=28408464}}</ref>
|Requires complex rearrangement due to incompatible orientation of genes with respect to chromosome arms
|-
|''[[ETV6]]''
|t(9;12)(q34;p13)
|''ETV6::ABL1''
|NO
|<ref>{{Cite journal|last=Zaliova|first=Marketa|last2=Moorman|first2=Anthony V.|last3=Cazzaniga|first3=Giovanni|last4=Stanulla|first4=Martin|last5=Harvey|first5=Richard C.|last6=Roberts|first6=Kathryn G.|last7=Heatley|first7=Sue L.|last8=Loh|first8=Mignon L.|last9=Konopleva|first9=Marina|date=2016-09|title=Characterization of leukemias with ETV6-ABL1 fusion|url=https://pubmed.ncbi.nlm.nih.gov/27229714|journal=Haematologica|volume=101|issue=9|pages=1082–1093|doi=10.3324/haematol.2016.144345|issn=1592-8721|pmc=5060025|pmid=27229714}}</ref>
|Requires complex rearrangement due to incompatible orientation of genes with respect to chromosome arms
|-
|''[[FOXP1]]''
|t(3;9)(p13;q34)
|''FOXP1::ABL1'' on der(3)
|YES
|<ref>{{Cite journal|last=Ernst|first=Thomas|last2=Score|first2=Joannah|last3=Deininger|first3=Michael|last4=Hidalgo-Curtis|first4=Claire|last5=Lackie|first5=Peter|last6=Ershler|first6=William B.|last7=Goldman|first7=John M.|last8=Cross|first8=Nicholas C. P.|last9=Grand|first9=Francish|date=2011-04|title=Identification of FOXP1 and SNX2 as novel ABL1 fusion partners in acute lymphoblastic leukaemia|url=https://pubmed.ncbi.nlm.nih.gov/21391972|journal=British Journal of Haematology|volume=153|issue=1|pages=43–46|doi=10.1111/j.1365-2141.2010.08457.x|issn=1365-2141|pmid=21391972}}</ref>
|
|-
|''LSM14A''
|t(9;19)(q34;q13.1)
|''LSM14A::ABL1'' on der(19)
|YES
|<ref name=":2" />
|
|-
|''NUP153''
|t(6;9)(p22.3;q34)
|''NUP153::ABL1'' on der(6)
|YES
|<ref name=":2" />
|
|-
|''[[NUP214]]''
|dup(9)(q34.1q34.1)
|''NUP214::ABL1''
|NO
|<ref>{{Cite journal|last=Duployez|first=Nicolas|last2=Grzych|first2=Guillaume|last3=Ducourneau|first3=Benoît|last4=Alarcon Fuentes|first4=Martin|last5=Grardel|first5=Nathalie|last6=Boyer|first6=Thomas|last7=Abou Chahla|first7=Wadih|last8=Bruno|first8=Bénédicte|last9=Nelken|first9=Brigitte|date=2016-04|title=NUP214-ABL1 fusion defines a rare subtype of B-cell precursor acute lymphoblastic leukemia that could benefit from tyrosine kinase inhibitors|url=https://pubmed.ncbi.nlm.nih.gov/26681761|journal=Haematologica|volume=101|issue=4|pages=e133–134|doi=10.3324/haematol.2015.136499|issn=1592-8721|pmc=5004396|pmid=26681761}}</ref>
|Tandem duplication (~370 kb) detectable by CMA
|-
|''RANBP2''
|t(2;9)(q12.3;q34)
|''RANBP::ABL1'' on der(2)
|YES
|<ref name=":9">{{Cite journal|last=Roberts|first=Kathryn G.|last2=Li|first2=Yongjin|last3=Payne-Turner|first3=Debbie|last4=Harvey|first4=Richard C.|last5=Yang|first5=Yung-Li|last6=Pei|first6=Deqing|last7=McCastlain|first7=Kelly|last8=Ding|first8=Li|last9=Lu|first9=Charles|date=2014-09-11|title=Targetable kinase-activating lesions in Ph-like acute lymphoblastic leukemia|url=https://pubmed.ncbi.nlm.nih.gov/25207766|journal=The New England Journal of Medicine|volume=371|issue=11|pages=1005–1015|doi=10.1056/NEJMoa1403088|issn=1533-4406|pmc=4191900|pmid=25207766}}</ref>
|
|-
|''RCSD1''
|t(1;9)(q24.2;q34)
|''RCSD1::ABL1'' on der(1)
|YES
|<ref>{{Cite journal|last=Collette|first=Y.|last2=Prébet|first2=T.|last3=Goubard|first3=A.|last4=Adélaïde|first4=J.|last5=Castellano|first5=R.|last6=Carbuccia|first6=N.|last7=Garnier|first7=S.|last8=Guille|first8=A.|last9=Arnoulet|first9=C.|date=2015-03-13|title=Drug response profiling can predict response to ponatinib in a patient with t(1;9)(q24;q34)-associated B-cell acute lymphoblastic leukemia|url=https://pubmed.ncbi.nlm.nih.gov/25768406|journal=Blood Cancer Journal|volume=5|issue=3|pages=e292|doi=10.1038/bcj.2015.13|issn=2044-5385|pmc=4382656|pmid=25768406}}</ref>
|
|-
|''SFPQ''
|t(1;9)(p34.3;q34)
|''SFPQ::ABL1'' on der(1)
|YES
|<ref>{{Cite journal|last=Sheng|first=Guangying|last2=Zeng|first2=Zhao|last3=Pan|first3=Jinlan|last4=Wang|first4=Qinrong|last5=Yao|first5=Hong|last6=Wen|first6=Lijun|last7=Ma|first7=Liang|last8=Wu|first8=Depei|last9=Chen|first9=Suning|date=2017|title=t(1;9)(p34;q34)/SFPQ-ABL1 Fusion in a Patient with Ph-Like Common B-Cell Acute Lymphoblastic Leukemia|url=https://pubmed.ncbi.nlm.nih.gov/27894117|journal=Acta Haematologica|volume=137|issue=1|pages=40–43|doi=10.1159/000452265|issn=1421-9662|pmid=27894117}}</ref>
|
|-
|''SNX1''
|t(9;15)(q34;q22.3)
|''SNX1::ABL1'' on der(15)
|YES
|<ref name=":10">{{Cite journal|last=Tasian|first=Sarah K.|last2=Loh|first2=Mignon L.|last3=Hunger|first3=Stephen P.|date=2017-11-09|title=Philadelphia chromosome-like acute lymphoblastic leukemia|url=https://pubmed.ncbi.nlm.nih.gov/28972016|journal=Blood|volume=130|issue=19|pages=2064–2072|doi=10.1182/blood-2017-06-743252|issn=1528-0020|pmc=5680607|pmid=28972016}}</ref>
|
|-
|''SNX2''
|t(5;9)(q23.2;q34)
|''SNX2::ABL1'' on der(5)
|YES
|<ref>{{Cite journal|last=Tomita|first=Osamu|last2=Iijima|first2=Kazutoshi|last3=Ishibashi|first3=Takeshi|last4=Osumi|first4=Tomoo|last5=Kobayashi|first5=Kenichiro|last6=Okita|first6=Hajime|last7=Saito|first7=Masahiro|last8=Mori|first8=Tetsuya|last9=Shimizu|first9=Toshiaki|date=2014-03|title=Sensitivity of SNX2-ABL1 toward tyrosine kinase inhibitors distinct from that of BCR-ABL1|url=https://pubmed.ncbi.nlm.nih.gov/24367893|journal=Leukemia Research|volume=38|issue=3|pages=361–370|doi=10.1016/j.leukres.2013.11.017|issn=1873-5835|pmid=24367893}}</ref>
|
|-
|''ZMIZ1''
|t(9;10)(q34;q22.3)
|''ZMIZ1::ABL1'' on der(10)
|YES
|<ref>{{Cite journal|last=Soler|first=G.|last2=Radford-Weiss|first2=I.|last3=Ben-Abdelali|first3=R.|last4=Mahlaoui|first4=N.|last5=Ponceau|first5=J. F.|last6=Macintyre|first6=E. A.|last7=Vekemans|first7=M.|last8=Bernard|first8=O. A.|last9=Romana|first9=S. P.|date=2008-06|title=Fusion of ZMIZ1 to ABL1 in a B-cell acute lymphoblastic leukaemia with a t(9;10)(q34;q22.3) translocation|url=https://pubmed.ncbi.nlm.nih.gov/18007576|journal=Leukemia|volume=22|issue=6|pages=1278–1280|doi=10.1038/sj.leu.2405033|issn=1476-5551|pmid=18007576}}</ref>
|
|-
| rowspan="3" |''[[ABL2]]''
(1q25.2)
|''PAG1''
|t(1;8)(q25.2;q21.1)
|''PAG1::ABL2'' on der(1)
|YES
|<ref name=":9" />
|
|-
|''RCSD1''
|1q24.2q25.2 rearrangement
|''RCSD1::ABL2''
|NO
|<ref>{{Cite journal|last=Raca|first=Gordana|last2=Gurbuxani|first2=Sandeep|last3=Zhang|first3=Zhiyu|last4=Li|first4=Zejuan|last5=Sukhanova|first5=Madina|last6=McNeer|first6=Jennifer|last7=Stock|first7=Wendy|date=2015-04|title=RCSD1-ABL2 fusion resulting from a complex chromosomal rearrangement in high-risk B-cell acute lymphoblastic leukemia|url=https://pubmed.ncbi.nlm.nih.gov/25098428|journal=Leukemia & Lymphoma|volume=56|issue=4|pages=1145–1147|doi=10.3109/10428194.2014.951851|issn=1029-2403|pmid=25098428}}</ref>
|On the same chromosome arm; however, a simple deletion cannot cause the fusion due to the orientation of genes
|-
|''ZC3HAV1''
|t(1;7)(q25.2;q34)
|''ZC3HAV1::ABL2'' on der(1)
|YES
|<ref>{{Cite journal|last=Tran|first=Thai Hoa|last2=Harris|first2=Marian H.|last3=Nguyen|first3=Jonathan V.|last4=Blonquist|first4=Traci M.|last5=Stevenson|first5=Kristen E.|last6=Stonerock|first6=Eileen|last7=Asselin|first7=Barbara L.|last8=Athale|first8=Uma H.|last9=Clavell|first9=Luis A.|date=2018-03-13|title=Prognostic impact of kinase-activating fusions and IKZF1 deletions in pediatric high-risk B-lineage acute lymphoblastic leukemia|url=https://pubmed.ncbi.nlm.nih.gov/29507076|journal=Blood Advances|volume=2|issue=5|pages=529–533|doi=10.1182/bloodadvances.2017014704|issn=2473-9537|pmc=5851421|pmid=29507076}}</ref>
|
|-
| rowspan="2" |''[[CRLF2]]''
(Xp22.3 & Yp11.3)
|''[[IGH]]''
|t(X;14)(p22.3;q32) or
t(Y;14)(p11.3;q32)
|''IGH::CRLF2''
|NO
|<ref name=":11">{{Cite journal|last=Jain|first=Nitin|last2=Roberts|first2=Kathryn G.|last3=Jabbour|first3=Elias|last4=Patel|first4=Keyur|last5=Eterovic|first5=Agda Karina|last6=Chen|first6=Ken|last7=Zweidler-McKay|first7=Patrick|last8=Lu|first8=Xinyan|last9=Fawcett|first9=Gloria|date=2017-02-02|title=Ph-like acute lymphoblastic leukemia: a high-risk subtype in adults|url=https://pubmed.ncbi.nlm.nih.gov/27919910|journal=Blood|volume=129|issue=5|pages=572–581|doi=10.1182/blood-2016-07-726588|issn=1528-0020|pmc=5290985|pmid=27919910}}</ref><ref name=":9" />
|
|-
|''P2RY8''
|del(X)(p22.3p22.3) or del(Y)(p11.3p11.3)
|''P2RY8::CRLF2''
|NO
|<ref name=":11" /><ref name=":9" />
|
|-
| rowspan="3" |''CSF1R''
(5q32)
|''MEF2D''
|t(1;5)(q22;q32)
|''MEF2D::CSF1R'' on der(5)
|YES
|<ref>{{Cite journal|last=Gu|first=Zhaohui|last2=Churchman|first2=Michelle|last3=Roberts|first3=Kathryn|last4=Li|first4=Yongjin|last5=Liu|first5=Yu|last6=Harvey|first6=Richard C.|last7=McCastlain|first7=Kelly|last8=Reshmi|first8=Shalini C.|last9=Payne-Turner|first9=Debbie|date=2016-11-08|title=Genomic analyses identify recurrent MEF2D fusions in acute lymphoblastic leukaemia|url=https://pubmed.ncbi.nlm.nih.gov/27824051|journal=Nature Communications|volume=7|pages=13331|doi=10.1038/ncomms13331|issn=2041-1723|pmc=5105166|pmid=27824051}}</ref>
|
|-
|''SSBP2''
|5q14.1q32 rearrangement
|''SSBP2::CSF1R''
|YES
|<ref name=":2" />
|On the same chromosome arm; however, a simple deletion cannot cause the fusion due to the orientation of genes
|-
|''TBL1XR1''
|t(3;5)(q26.3;q32)
|''TBL1XR1::CSF1R'' on der(5)
|YES
|<ref name=":2" />
|
|-
|''DGKH'' (13q14.1)
|''ZFAND3''
|t(6;13)(p21.2;q14.1)
|''ZFAND3::DGKH''
|YES
|<ref name=":9" />
|Requires complex rearrangement due to incompatible orientation of genes with respect to chromosome arms
|-
| rowspan="4" |''EPOR'' (19p13.2)
|''[[IGH]]''
|ins(14;19)(q32;p13.2p13.2)
|''IGH/EPOR''
|Cryptic insertion
|<ref name=":12">{{Cite journal|last=Iacobucci|first=Ilaria|last2=Li|first2=Yongjin|last3=Roberts|first3=Kathryn G.|last4=Dobson|first4=Stephanie M.|last5=Kim|first5=Jaeseung C.|last6=Payne-Turner|first6=Debbie|last7=Harvey|first7=Richard C.|last8=Valentine|first8=Marcus|last9=McCastlain|first9=Kelly|date=2016-02-08|title=Truncating Erythropoietin Receptor Rearrangements in Acute Lymphoblastic Leukemia|url=https://pubmed.ncbi.nlm.nih.gov/26859458|journal=Cancer Cell|volume=29|issue=2|pages=186–200|doi=10.1016/j.ccell.2015.12.013|issn=1878-3686|pmc=4750652|pmid=26859458}}</ref>
|
|-
|''IGK''
|ins(2;19)(p11.2;p13.2p13.2)
|''IGK/EPOR''
|Cryptic insertion
|<ref name=":12" />
|
|-
|''LAIR1''
|inv(19)(p13.2q13.42)
|''LAIR1::EPOR''
|NO
|<ref name=":12" />
|Inversion of chromosome 19 juxtaposes ''EPOR'' to the upstream region of ''LAIR1''
|-
|''THADA''
|t(2;19)(p21;p13.2)
|''THADA::EPOR''
|YES
|<ref name=":10" />
|
|-
|''IL2RB'' (22q12.3)
|''MYH9''
|22q12.3 rearrangement
|''MYH9::IL2RB''
|NO
|<ref name=":9" />
|On the same chromosome arm; however, a simple deletion cannot cause the fusion due to the orientation of genes
|-
| rowspan="22" |''[[JAK2]]''
(9p24.1)
|''ATF7IP''
|t(9;12)(p24.1;p13.1)
|''ATF7IP::JAK2'' on der(9)
|NO
|<ref name=":9" /><ref>{{Cite journal|last=Zhang|first=Qi|last2=Shi|first2=Ce|last3=Han|first3=Lina|last4=Jain|first4=Nitin|last5=Roberts|first5=Kathryn G.|last6=Ma|first6=Helen|last7=Cai|first7=Tianyu|last8=Cavazos|first8=Antonio|last9=Tabe|first9=Yoko|date=2018-01-30|title=Inhibition of mTORC1/C2 signaling improves anti-leukemia efficacy of JAK/STAT blockade in CRLF2 rearranged and/or JAK driven Philadelphia chromosome-like acute B-cell lymphoblastic leukemia|url=https://pubmed.ncbi.nlm.nih.gov/29487712|journal=Oncotarget|volume=9|issue=8|pages=8027–8041|doi=10.18632/oncotarget.24261|issn=1949-2553|pmc=5814279|pmid=29487712}}</ref>
|
|-
|''[[BCR]]''
|t(9;22)(p24.1;q11.2)
|''BCR::JAK2''
|? YES
|<ref>{{Cite journal|last=Griesinger|first=Frank|last2=Hennig|first2=Heike|last3=Hillmer|first3=Frauke|last4=Podleschny|first4=Martina|last5=Steffens|first5=Rainer|last6=Pies|first6=Andreas|last7=Wörmann|first7=Bernhard|last8=Haase|first8=Detlef|last9=Bohlander|first9=Stefan K.|date=2005-11|title=A BCR-JAK2 fusion gene as the result of a t(9;22)(p24;q11.2) translocation in a patient with a clinically typical chronic myeloid leukemia|url=https://pubmed.ncbi.nlm.nih.gov/16001431|journal=Genes, Chromosomes & Cancer|volume=44|issue=3|pages=329–333|doi=10.1002/gcc.20235|issn=1045-2257|pmid=16001431}}</ref>
|Seen also in myeloproliferative neoplasms. Requires complex rearrangement due to incompatible orientation of genes with respect to chromosome arms
|-
|''EBF1''
|t(5;9)(q33.3;p24.1)
|''EBF1::JAK2'' on der(9)
|NO (SUBTLE)
|<ref name=":13">{{Cite journal|last=Roberts|first=Kathryn G.|last2=Yang|first2=Yung-Li|last3=Payne-Turner|first3=Debbie|last4=Lin|first4=Wenwei|last5=Files|first5=Jacob K.|last6=Dickerson|first6=Kirsten|last7=Gu|first7=Zhaohui|last8=Taunton|first8=Jack|last9=Janke|first9=Laura J.|date=2017-09-12|title=Oncogenic role and therapeutic targeting of ABL-class and JAK-STAT activating kinase alterations in Ph-like ALL|url=https://pubmed.ncbi.nlm.nih.gov/29296813|journal=Blood Advances|volume=1|issue=20|pages=1657–1671|doi=10.1182/bloodadvances.2017011296|issn=2473-9529|pmc=5728345|pmid=29296813}}</ref>
|
|-
|''[[ETV6]]''
|t(9;12)(p24.1;p13.2)
|''ETV6::JAK2'' on der(9)
|NO (SUBTLE)
|<ref>{{Cite journal|last=Zhou|first=Min-hang|last2=Gao|first2=Li|last3=Jing|first3=Yu|last4=Xu|first4=Yuan-yuan|last5=Ding|first5=Yi|last6=Wang|first6=Nan|last7=Wang|first7=Wei|last8=Li|first8=Mian-yang|last9=Han|first9=Xiao-ping|date=2012-08|title=Detection of ETV6 gene rearrangements in adult acute lymphoblastic leukemia|url=https://pubmed.ncbi.nlm.nih.gov/22373549|journal=Annals of Hematology|volume=91|issue=8|pages=1235–1243|doi=10.1007/s00277-012-1431-4|issn=1432-0584|pmid=22373549}}</ref><ref>{{Cite journal|last=Schwaller|first=Jurg|date=2012-12|title=Modeling ETV6-JAK2-induced leukemia: insights from the zebrafish|url=https://pubmed.ncbi.nlm.nih.gov/23204479|journal=Haematologica|volume=97|issue=12|pages=1783–1785|doi=10.3324/haematol.2012.080754|issn=1592-8721|pmc=3590083|pmid=23204479}}</ref>
|
|-
|''GOLGA5''
|t(9;14)(p24.1;q32.1)
|''GOLGA5::JAK2''
|NO (SUBTLE)
|<ref>{{Cite journal|last=Ding|first=Yang Y.|last2=Stern|first2=Julie W.|last3=Jubelirer|first3=Tracey F.|last4=Wertheim|first4=Gerald B.|last5=Lin|first5=Fumin|last6=Chang|first6=Fengqi|last7=Gu|first7=Zhaohui|last8=Mullighan|first8=Charles G.|last9=Li|first9=Yong|date=2018-09|title=Clinical efficacy of ruxolitinib and chemotherapy in a child with Philadelphia chromosome-like acute lymphoblastic leukemia with GOLGA5-JAK2 fusion and induction failure|url=https://pubmed.ncbi.nlm.nih.gov/29773603|journal=Haematologica|volume=103|issue=9|pages=e427–e431|doi=10.3324/haematol.2018.192088|issn=1592-8721|pmc=6119161|pmid=29773603}}</ref>
|Requires complex rearrangement due to incompatible orientation of genes with respect to chromosome arms
|-
|''HMBOX1''
|t(8;9)(p21.1;p24.1)
|''HMBOX1::JAK2'' on der(9)
|YES
|<ref name=":14">{{Cite journal|last=Roberts|first=Kathryn G.|last2=Gu|first2=Zhaohui|last3=Payne-Turner|first3=Debbie|last4=McCastlain|first4=Kelly|last5=Harvey|first5=Richard C.|last6=Chen|first6=I.-Ming|last7=Pei|first7=Deqing|last8=Iacobucci|first8=Ilaria|last9=Valentine|first9=Marcus|date=2017-02|title=High Frequency and Poor Outcome of Philadelphia Chromosome-Like Acute Lymphoblastic Leukemia in Adults|url=https://pubmed.ncbi.nlm.nih.gov/27870571|journal=Journal of Clinical Oncology: Official Journal of the American Society of Clinical Oncology|volume=35|issue=4|pages=394–401|doi=10.1200/JCO.2016.69.0073|issn=1527-7755|pmc=5455698|pmid=27870571}}</ref>
|
|-
|''OFD1''
|t(X;9)(p22.2;p24.1)
|''OFD1::JAK2'' on der(9)
|NO (SUBTLE)
|<ref>{{Cite journal|last=Yano|first=Mio|last2=Imamura|first2=Toshihiko|last3=Asai|first3=Daisuke|last4=Kiyokawa|first4=Nobutaka|last5=Nakabayashi|first5=Kazuhiko|last6=Matsumoto|first6=Kenji|last7=Deguchi|first7=Takao|last8=Hashii|first8=Yoshiko|last9=Honda|first9=Yu-ko|date=2015-12|title=Identification of novel kinase fusion transcripts in paediatric B cell precursor acute lymphoblastic leukaemia with IKZF1 deletion|url=https://pubmed.ncbi.nlm.nih.gov/26404892|journal=British Journal of Haematology|volume=171|issue=5|pages=813–817|doi=10.1111/bjh.13757|issn=1365-2141|pmid=26404892}}</ref>
|
|-
|''PAX5''
|inv(9)(p13.2p24.1)
|''PAX5::JAK2''
|YES
|<ref>{{Cite journal|last=Schinnerl|first=Dagmar|last2=Fortschegger|first2=Klaus|last3=Kauer|first3=Maximilian|last4=Marchante|first4=João R. M.|last5=Kofler|first5=Reinhard|last6=Den Boer|first6=Monique L.|last7=Strehl|first7=Sabine|date=2015-02-19|title=The role of the Janus-faced transcription factor PAX5-JAK2 in acute lymphoblastic leukemia|url=https://pubmed.ncbi.nlm.nih.gov/25515960|journal=Blood|volume=125|issue=8|pages=1282–1291|doi=10.1182/blood-2014-04-570960|issn=1528-0020|pmc=4375719|pmid=25515960}}</ref>
|An inversion is required as genes are oriented in opposite directions
|-
|''[[PCM1]]''
|t(8;9)(p22;p24.1)
|''PCM1::JAK2'' on der(9)
|YES (SUBTLE)
|<ref name=":10" />
|Seen also in myeloid/lymphoid neoplasms with eosinophilia
|-
|''PPFIBP1''
|t(9;12)(p24.1;p11.2)
|''PPFIBP1::JAK2'' on der(9)
|YES
|<ref name=":10" />
|
|-
|''RFX3''
|inv(9)(p24.1p24.2)
|''RFX3::JAK2''
|NO
|<ref name=":2" />
|An inversion is required as genes are oriented in opposite directions
|-
|''SMU1''
|inv(9)(p21.1p24.1)
|''SMU1::JAK2''
|NO
|<ref name=":14" />
|An inversion is required as genes are oriented in opposite directions
|-
|''SNX29''
|t(9;16)(p24.1;p13.1)
|''SNX29::JAK2'' on der(9)
|YES
|<ref name=":14" />
|
|-
|''SPAG9''
|t(9;17)(p24.1;q21.3)
|''SPAG9::JAK2'' on der(9)
|YES
|<ref>{{Cite journal|last=Kawamura|first=Machiko|last2=Taki|first2=Tomohiko|last3=Kaku|first3=Hidefumi|last4=Ohki|first4=Kentaro|last5=Hayashi|first5=Yasuhide|date=2015-07|title=Identification of SPAG9 as a novel JAK2 fusion partner gene in pediatric acute lymphoblastic leukemia with t(9;17)(p24;q21)|url=https://pubmed.ncbi.nlm.nih.gov/25951811|journal=Genes, Chromosomes & Cancer|volume=54|issue=7|pages=401–408|doi=10.1002/gcc.22251|issn=1098-2264|pmid=25951811}}</ref>
|
|-
|''SSBP2''
|t(5;9)(q14.1;p24.1)
|''SSBP2::JAK2'' on der(9)
|YES
|<ref>{{Cite journal|last=Poitras|first=Jennifer L.|last2=Dal Cin|first2=Paola|last3=Aster|first3=Jon C.|last4=Deangelo|first4=Daniel J.|last5=Morton|first5=Cynthia C.|date=2008-10|title=Novel SSBP2-JAK2 fusion gene resulting from a t(5;9)(q14.1;p24.1) in pre-B acute lymphocytic leukemia|url=https://pubmed.ncbi.nlm.nih.gov/18618714|journal=Genes, Chromosomes & Cancer|volume=47|issue=10|pages=884–889|doi=10.1002/gcc.20585|issn=1098-2264|pmid=18618714}}</ref>
|
|-
|''STRN3''
|t(9;14)(p24.1;q12)
|''STRN3::JAK2'' on der(9)
|YES
|<ref>{{Cite journal|last=Roberts|first=Kathryn G.|last2=Morin|first2=Ryan D.|last3=Zhang|first3=Jinghui|last4=Hirst|first4=Martin|last5=Zhao|first5=Yongjun|last6=Su|first6=Xiaoping|last7=Chen|first7=Shann-Ching|last8=Payne-Turner|first8=Debbie|last9=Churchman|first9=Michelle L.|date=2012-08-14|title=Genetic alterations activating kinase and cytokine receptor signaling in high-risk acute lymphoblastic leukemia|url=https://pubmed.ncbi.nlm.nih.gov/22897847|journal=Cancer Cell|volume=22|issue=2|pages=153–166|doi=10.1016/j.ccr.2012.06.005|issn=1878-3686|pmc=3422513|pmid=22897847}}</ref>
|
|-
|''TERF2''
|t(9;16)(p24.1;q22.1)
|''TERF2::JAK2'' on der(9)
|YES
|<ref>{{Cite journal|last=Steeghs|first=Elisabeth M. P.|last2=Jerchel|first2=Isabel S.|last3=de Goffau-Nobel|first3=Willemieke|last4=Hoogkamer|first4=Alex Q.|last5=Boer|first5=Judith M.|last6=Boeree|first6=Aurélie|last7=van de Ven|first7=Cesca|last8=Koudijs|first8=Marco J.|last9=Besselink|first9=Nicolle J. M.|date=2017-10-27|title=JAK2 aberrations in childhood B-cell precursor acute lymphoblastic leukemia|url=https://pubmed.ncbi.nlm.nih.gov/29163799|journal=Oncotarget|volume=8|issue=52|pages=89923–89938|doi=10.18632/oncotarget.21027|issn=1949-2553|pmc=5685720|pmid=29163799}}</ref>
|
|-
|''TPR''
|t(1;9)(q31.1;p24.1)
|''TPR::JAK2'' on der(9)
|YES
|<ref name=":9" />
|
|-
|''USP25''
|t(9;21)(p24.1;q21.1)
|''USP25::JAK2''
|? YES
|<ref name=":2" />
|Requires complex rearrangement due to incompatible orientation of genes with respect to chromosome arms
|-
|''ZBTB46''
|t(9;20)(p24.1;q13.3)
|''ZBTB46::JAK2'' on der(9)
|NO
|<ref name=":10" />
|
|-
|''ZNF274''
|t(9;19)(p24.1;q13.4)
|''ZNF274::JAK2''
|NO
|<ref name=":2" />
|Requires complex rearrangement due to incompatible orientation of genes with respect to chromosome arms
|-
|''ZNF340''
|t(9;20)(p24.1;q13.3)
|''ZNF340::JAK2'' on der(9)
|NO
|<ref name=":10" />
|
|-
|''[[PDGFRA]]''
(4q12)
|''FIP1L1''
|del(4)(q12q12)
|''FIP1L1::PDGFRA''
|NO
|<ref name=":14" />
|Interstitial deletion. Seen also in myeloid/lymphoid neoplasms with eosinophilia
|-
| rowspan="8" |''[[PDGFRB]]'' (5q32)
|''ATF7IP''
|t(5;12)(q32;p13.1)
|''ATF7IP::PDGFRB'' on der(5)
|YES
|<ref>{{Cite journal|last=Kobayashi|first=Kenichiro|last2=Mitsui|first2=Kazumasa|last3=Ichikawa|first3=Hitoshi|last4=Nakabayashi|first4=Kazuhiko|last5=Matsuoka|first5=Masaki|last6=Kojima|first6=Yasuko|last7=Takahashi|first7=Hiroyuki|last8=Iijima|first8=Kazutoshi|last9=Ootsubo|first9=Kaori|date=2014-06|title=ATF7IP as a novel PDGFRB fusion partner in acute lymphoblastic leukaemia in children|url=https://pubmed.ncbi.nlm.nih.gov/24628626|journal=British Journal of Haematology|volume=165|issue=6|pages=836–841|doi=10.1111/bjh.12834|issn=1365-2141|pmid=24628626}}</ref><ref>{{Cite journal|last=Ishibashi|first=Takeshi|last2=Yaguchi|first2=Akinori|last3=Terada|first3=Kazuki|last4=Ueno-Yokohata|first4=Hitomi|last5=Tomita|first5=Osamu|last6=Iijima|first6=Kazutoshi|last7=Kobayashi|first7=Kenichiro|last8=Okita|first8=Hajime|last9=Fujimura|first9=Junya|date=2016-03|title=Ph-like ALL-related novel fusion kinase ATF7IP-PDGFRB exhibits high sensitivity to tyrosine kinase inhibitors in murine cells|url=https://pubmed.ncbi.nlm.nih.gov/26703895|journal=Experimental Hematology|volume=44|issue=3|pages=177–188.e5|doi=10.1016/j.exphem.2015.11.009|issn=1873-2399|pmid=26703895}}</ref><ref>{{Cite journal|last=Zhang|first=Ge|last2=Zhang|first2=Yanle|last3=Wu|first3=Jianrong|last4=Chen|first4=Yan|last5=Ma|first5=Zhigui|date=2017-11-14|title=Acute Lymphoblastic Leukemia Patient with Variant ATF7IP/PDGFRB Fusion and Favorable Response to Tyrosine Kinase Inhibitor Treatment: A Case Report|url=https://pubmed.ncbi.nlm.nih.gov/29133777|journal=The American Journal of Case Reports|volume=18|pages=1204–1208|doi=10.12659/ajcr.906300|issn=1941-5923|pmc=5700447|pmid=29133777}}</ref>
|
|-
|''EBF1''
|del(5)(q32q33.3)
|''EBF1::PDGFRB''
|NO
|<ref>{{Cite journal|last=Schwab|first=Claire|last2=Ryan|first2=Sarra L.|last3=Chilton|first3=Lucy|last4=Elliott|first4=Alannah|last5=Murray|first5=James|last6=Richardson|first6=Stacey|last7=Wragg|first7=Christopher|last8=Moppett|first8=John|last9=Cummins|first9=Michelle|date=2016-05-05|title=EBF1-PDGFRB fusion in pediatric B-cell precursor acute lymphoblastic leukemia (BCP-ALL): genetic profile and clinical implications|url=https://pubmed.ncbi.nlm.nih.gov/26872634|journal=Blood|volume=127|issue=18|pages=2214–2218|doi=10.1182/blood-2015-09-670166|issn=1528-0020|pmid=26872634}}</ref>
|Interstitial deletion
|-
|''[[ETV6]]''
|t(5;12)(q32;p13.2)
|''ETV6::PDGFRB'' on der(5)
|YES
|<ref name=":10" />
|
|-
|''SNX29''
|t(5;16)(q32;p13.1)
|''SNX29::PDGFRB'' on der(5)
|YES
|<ref name=":10" />
|
|-
|''SSBP2''
|t(5;5)(q14.1;q32)
|''SSBP2::PDGFRB''
|? YES
|<ref name=":10" />
|On the same chromosome arm; however, a simple deletion cannot cause the fusion due to the orientation of genes
|-
|''TNIP1''
|del(5)(q32q33.1)
|''TNIP1::PDGFRB''
|NO
|<ref name=":10" />
|Interstitial deletion. Seen also in myeloid/lymphoid neoplasms with eosinophilia
|-
|''ZEB2''
|t(2;5)(q22.3;q32)
|''ZEB2::PDGFRB'' on der(5)
|YES
|<ref name=":9" />
|
|-
|''ZMYND8''
|t(5;20)(q32;q13.1)
|''ZMYND8::PDGFRB'' on der(5)
|YES
|<ref name=":2" />
|
|-
| rowspan="3" |''PTK2B'' (8p21.2)
|''[[KDM6A]]''
|t(X;8)(p11.3;p21.2)
|''KDM6A::PTK2B'' on der(8)
|YES
|<ref name=":9" />
|
|-
|-
!Finding!!Marker
|''[[STAG2]]''
|t(X;8)(q25;p21.2)
|''STAG2::PTK2B''
|YES
|<ref name=":9" />
|Requires complex rearrangement due to incompatible orientation of genes with respect to chromosome arms
|-
|-
|Positive (universal)||<span class="blue-text">EXAMPLE:</span> CD1
|''TMEM2''
|t(8;9)(p21.2;q21.1)
|''TMEM2::PTK2B'' on der(8)
|YES
|<ref name=":10" />
|
|-
|-
|Positive (subset)||<span class="blue-text">EXAMPLE:</span> CD2
| rowspan="3" |''TYK2'' (19p13.2)
|''MYB''
|t(6;19)(q23.3;p13.2)
|''MYB::TYK2'' on der(6)
|YES
|<ref name=":13" />
|
|-
|-
|Negative (universal)||<span class="blue-text">EXAMPLE:</span> CD3
|''SMARCA4''
|inv(19)(p13.2p13.2)
|''SMARCA4::TYK2''
|NO
|<ref name=":10" />
|
|-
|-
|Negative (subset)||<span class="blue-text">EXAMPLE:</span> CD4
|''ZNF340''
|t(19;20)(p13.2;q13.3)
|''ZNF340::TYK2''
|NO
|<ref name=":10" />
|Requires complex rearrangement due to incompatible orientation of genes with respect to chromosome arms
|}
|}


 
==Individual Region Genomic Gain/Loss/LOH==
<blockquote class='blockedit'>{{Box-round|title=v4:Immunophenotype|The content below was from the old template. Please incorporate above.}}</blockquote>
Blasts are typically CD19, TdT, and CD10-positive. By flow cytometry, a subset of cases with CRLF2 translocations show very high levels of surface protein expression<ref name=":2" />.
 
<blockquote class="blockedit">
<center><span style="color:Maroon">'''End of V4 Section'''</span>
----
</blockquote>
==Chromosomal Rearrangements (Gene Fusions)==
 
Put your text here and fill in the table


{| class="wikitable sortable"
{| class="wikitable sortable"
|-
|-
!Chromosomal Rearrangement!!Genes in Fusion (5’ or 3’ Segments)!!Pathogenic Derivative!!Prevalence
!Chr #!!Gain, Loss, Amp, LOH!!Minimal Region Cytoband and/or Genomic Coordinates [Genome Build; Size]!!Relevant Gene(s)
!Diagnostic Significance (Yes, No or Unknown)
!Diagnostic, Prognostic, and Therapeutic Significance - D, P, T
!Prognostic Significance (Yes, No or Unknown)
!Established Clinical Significance Per Guidelines - Yes or No (Source)
!Therapeutic Significance (Yes, No or Unknown)
!Clinical Relevance Details/Other Notes
!Notes
|-
|-
|<span class="blue-text">EXAMPLE:</span> t(9;22)(q34;q11.2)||<span class="blue-text">EXAMPLE:</span> 3'ABL1 / 5'BCR||<span class="blue-text">EXAMPLE:</span> der(22)||<span class="blue-text">EXAMPLE:</span> 20% (COSMIC)
|5
<span class="blue-text">EXAMPLE:</span> 30% (add reference)
|Loss
|Yes
|chr5:158,695,920-159,099,916
[GRCh38/hg38]
|''EBF1''
|Unknown
|No
|No
|Yes
|Deletion of ''EBF1'' results in altered B-cell development.<ref name=":4">{{Cite journal|last=Boer|first=Judith M.|last2=Marchante|first2=João R. M.|last3=Evans|first3=William E.|last4=Horstmann|first4=Martin A.|last5=Escherich|first5=Gabriele|last6=Pieters|first6=Rob|last7=Den Boer|first7=Monique L.|date=2015-09|title=BCR-ABL1-like cases in pediatric acute lymphoblastic leukemia: a comparison between DCOG/Erasmus MC and COG/St. Jude signatures|url=https://pubmed.ncbi.nlm.nih.gov/26045294|journal=Haematologica|volume=100|issue=9|pages=e354–357|doi=10.3324/haematol.2015.124941|issn=1592-8721|pmc=4800707|pmid=26045294}}</ref>
|<span class="blue-text">EXAMPLE:</span>
 
The t(9;22) is diagnostic of CML in the appropriate morphology and clinical context (add reference). This fusion is responsive to targeted therapy such as Imatinib (Gleevec) (add reference).
|}
 
<blockquote class='blockedit'>{{Box-round|title=v4:Chromosomal Rearrangements (Gene Fusions)|The content below was from the old template. Please incorporate above.}}</blockquote>
Tyrosine kinase-type translocations are common and involve ''ABL1'' and other kinases (such as ''ABL2'', ''EPOR'', ''JAK2'', ''PDGFRB'', and ''CSF1R''); more than 30 gene partners have been described. Frequently reported examples include ''IGH''–''EPOR'' of the t(14;19)(q32;p13)/ins(14;19)(q32;p13), ''EBF1''–''PDGFRB'' of the del(5)(q32q33.3), ''NUP214''–''ABL1'' of the t(9;9)(q34;q34)/del(9)(q34q34), and ''ETV6''–''ABL1'' of the t(9;12)(q34;p13). Other notable fusions are ''BCR''–''JAK2'', ''PAX5''–''JAK2'', ''STRN3''–''JAK2'', ''RANBP2''–''ABL1'', ''RCSD1''–''ABL1'', and ''MEF2D''–''CSF1R''<ref>Heim S & Mitelman F. Cancer Cytogenetics: Chromosomal and Molecular Genetic Aberrations of Tumor Cells. John Wiley & Sons, Incorporated: Chichester, United Kingdom. 2015.</ref>.
 
<blockquote class="blockedit">
<center><span style="color:Maroon">'''End of V4 Section'''</span>
----
</blockquote>
 
 
<blockquote class='blockedit'>{{Box-round|title=v4:Clinical Significance (Diagnosis, Prognosis and Therapeutic Implications).|Please incorporate this section into the relevant tables found in:
* Chromosomal Rearrangements (Gene Fusions)
* Individual Region Genomic Gain/Loss/LOH
* Characteristic Chromosomal Patterns
* Gene Mutations (SNV/INDEL)}}</blockquote>
 
*Diagnosis:  Definitive diagnosis is based on two major gene expression signatures (DCOG/Erasmus MC and COG/St. Jude).
**DCOG/Erasmus MC incorporates hierarchal clustering of microarrays using a 110-gene probe set; this genetic signature frequently detected deletions in ''IKZF1'', dic(9;20), and iAMP21 in BCR-ABL1-like B-ALL<ref name=":0" />.
**COG/St. Jude employs predictive analysis of microarrays using a 257-gene probe set; this genetic signature demonstrated primarily activating kinase or cytokine receptor signaling alterations, in addition to ''IKZF1'' deletions<ref name=":1" />.
*Prognosis:  In both pediatric and adult populations, BCR-ABL1-like B-ALL is associated with high rates of relapse and poor prognosis.
**The median 5-year overall survival rates for children with BCR-ABL1-like B-ALL, adolescents, and young adults was 72.8%, 65.8%, and 25.8%, respectively<ref name=":4" />.
**Median 5-year-overall survival in adults was 22%, versus 64% in comparable patients with non-BCR-ABL1, non-BCR-ABL1-like, and non-MLL translocation B-ALL<ref name=":5" />.
*Therapeutic Implications:  Due to the aggressive nature of the disease, patients are often treated with high-intensity chemotherapy regimens, such as hyper-CVAD or an augmented Berlin-Frankfurt-Münster regimen<ref name=":6" />.
**However, given the high incidence of fusions involving ''JAK2'', ''ABL1'', ''ABL2'', and other tyrosine kinases, tyrosine kinase inhibitors and JAK inhibitors are now being trialed clinically<ref name=":4" /><ref>{{Cite journal|last=Tasian|first=Sarah K.|last2=Doral|first2=Michelle Y.|last3=Borowitz|first3=Michael J.|last4=Wood|first4=Brent L.|last5=Chen|first5=I.-Ming|last6=Harvey|first6=Richard C.|last7=Gastier-Foster|first7=Julie M.|last8=Willman|first8=Cheryl L.|last9=Hunger|first9=Stephen P.|date=2012|title=Aberrant STAT5 and PI3K/mTOR pathway signaling occurs in human CRLF2-rearranged B-precursor acute lymphoblastic leukemia|url=https://www.ncbi.nlm.nih.gov/pubmed/22685175|journal=Blood|volume=120|issue=4|pages=833–842|doi=10.1182/blood-2011-12-389932|issn=1528-0020|pmc=3412346|pmid=22685175}}</ref><ref>{{Cite journal|last=Iacobucci|first=Ilaria|last2=Li|first2=Yongjin|last3=Roberts|first3=Kathryn G.|last4=Dobson|first4=Stephanie M.|last5=Kim|first5=Jaeseung C.|last6=Payne-Turner|first6=Debbie|last7=Harvey|first7=Richard C.|last8=Valentine|first8=Marcus|last9=McCastlain|first9=Kelly|date=2016|title=Truncating Erythropoietin Receptor Rearrangements in Acute Lymphoblastic Leukemia|url=https://www.ncbi.nlm.nih.gov/pubmed/26859458|journal=Cancer Cell|volume=29|issue=2|pages=186–200|doi=10.1016/j.ccell.2015.12.013|issn=1878-3686|pmc=4750652|pmid=26859458}}</ref>.
 
<blockquote class="blockedit">
<center><span style="color:Maroon">'''End of V4 Section'''</span>
----
</blockquote>
==Individual Region Genomic Gain / Loss / LOH==
 
Put your text here and fill in the table <span style="color:#0070C0">(''Instructions: Includes aberrations not involving gene fusions. Can include references in the table. Can refer to CGC workgroup tables as linked on the homepage if applicable. Do not delete table.'') </span>
 
{| class="wikitable sortable"
|-
|-
!Chr #!!Gain / Loss / Amp / LOH!!Minimal Region Genomic Coordinates [Genome Build]!!Minimal Region Cytoband
|7
!Diagnostic Significance (Yes, No or Unknown)
|Loss
!Prognostic Significance (Yes, No or Unknown)
|chr7:50,303,455-50,405,101
!Therapeutic Significance (Yes, No or Unknown)
[GRCh38/hg38]
!Notes
|''IKZF1''
|P
|Yes, [https://www.nccn.org/professionals/physician_gls/pdf/all.pdf NCCN - Acute Lymphoblastic leukaemia]
|Monoallelic (often partial) deletion of the IKAROS transcription factor, encoded by ''IKZF1'', is one of the most frequently observed genetic abnormalities in B-lymphoblastic leukaemia/lymphoma with ''BCR::ABL1''-like features, although this finding is not specific and not included in the definition;<ref name=":3">{{Cite journal|last=Boer|first=Judith M.|last2=Marchante|first2=João R. M.|last3=Evans|first3=William E.|last4=Horstmann|first4=Martin A.|last5=Escherich|first5=Gabriele|last6=Pieters|first6=Rob|last7=Den Boer|first7=Monique L.|date=2015|title=BCR-ABL1-like cases in pediatric acute lymphoblastic leukemia: a comparison between DCOG/Erasmus MC and COG/St. Jude signatures|url=https://www.ncbi.nlm.nih.gov/pubmed/26045294|journal=Haematologica|volume=100|issue=9|pages=e354–357|doi=10.3324/haematol.2015.124941|issn=1592-8721|pmc=4800707|pmid=26045294}}</ref> ''IKZF1'' deletion is associated with poor prognosis.<ref>{{Cite journal|last=van der Veer|first=Arian|last2=Waanders|first2=Esmé|last3=Pieters|first3=Rob|last4=Willemse|first4=Marieke E.|last5=Van Reijmersdal|first5=Simon V.|last6=Russell|first6=Lisa J.|last7=Harrison|first7=Christine J.|last8=Evans|first8=William E.|last9=van der Velden|first9=Vincent H. J.|date=2013-10-10|title=Independent prognostic value of BCR-ABL1-like signature and IKZF1 deletion, but not high CRLF2 expression, in children with B-cell precursor ALL|url=https://pubmed.ncbi.nlm.nih.gov/23974192|journal=Blood|volume=122|issue=15|pages=2622–2629|doi=10.1182/blood-2012-10-462358|issn=1528-0020|pmc=3795461|pmid=23974192}}</ref>
|-
|-
|<span class="blue-text">EXAMPLE:</span>
|9
|Loss
|chr9:21,967,752-21,995,324
chr9:22,002,903-22,009,313


7
[GRCh38/hg38]
|<span class="blue-text">EXAMPLE:</span> Loss
|''CDKN2A''
|<span class="blue-text">EXAMPLE:</span>
''CDKN2B''
 
|Unknown
chr7:1- 159,335,973 [hg38]
|No
|<span class="blue-text">EXAMPLE:</span>
|Deletion of ''CDKN2A/B'' results in altered B-cell development.<ref name=":4" />
 
|-
chr7
|9
|Yes
|Loss
|Yes
|chr9:36,833,269-37,034,268
[GRCh38/hg38]
|''PAX5''
|Unknown
|No
|No
|<span class="blue-text">EXAMPLE:</span>
|Deletion of ''PAX5'' results in altered B-cell development.<ref name=":4" />
 
Presence of monosomy 7 (or 7q deletion) is sufficient for a diagnosis of AML with MDS-related changes when there is ≥20% blasts and no prior therapy (add reference).  Monosomy 7/7q deletion is associated with a poor prognosis in AML (add reference).
|-
|-
|<span class="blue-text">EXAMPLE:</span>
|12
 
|Loss
8
|chr12:11,649,674-11,895,377
|<span class="blue-text">EXAMPLE:</span> Gain
[GRCh38/hg38]
|<span class="blue-text">EXAMPLE:</span>
|''ETV6''
 
|Unknown
chr8:1-145,138,636 [hg38]
|<span class="blue-text">EXAMPLE:</span>
 
chr8
|No
|No
|Deletion of ''ETV6'' results in altered B-cell development.<ref name=":4" />
|-
|13
|Loss
|chr13:48,303,744-48,599,436
[GRCh38/hg38]
|''RB1''
|Unknown
|No
|No
|Deletion of ''RB1'' results in disrupted cell-cycle regulation.<ref name=":4" />
|-
|17
|Loss
|chr17:7,661,779-7,687,546
[GRCh38/hg38]
|''TP53''
|Unknown
|No
|No
|<span class="blue-text">EXAMPLE:</span>
|Deletion of ''TP53'' results in in disrupted cell-cycle regulation.<ref name=":4" />
 
Common recurrent secondary finding for t(8;21) (add reference).
|}
|}


<blockquote class='blockedit'>{{Box-round|title=v4:Genomic Gain/Loss/LOH|The content below was from the old template. Please incorporate above.}}</blockquote>
==Characteristic Chromosomal or Other Global Mutational Patterns==
Monoallelic (often partial) deletion of the IKAROS transcription factor, encoded by ''IKZF1'', is one of the most frequently observed genetic abnormalities in BCR-ABL1-like B-ALL, although this finding is not specific and not included in the definition<ref name=":3" />.
<blockquote class="blockedit">
<center><span style="color:Maroon">'''End of V4 Section'''</span>
----
</blockquote>
==Characteristic Chromosomal Patterns==
 
Put your text here <span style="color:#0070C0">(''EXAMPLE PATTERNS: hyperdiploid; gain of odd number chromosomes including typically chromosome 1, 3, 5, 7, 11, and 17; co-deletion of 1p and 19q; complex karyotypes without characteristic genetic findings; chromothripsis. Do not delete table.'')</span>


{| class="wikitable sortable"
{| class="wikitable sortable"
|-
|-
!Chromosomal Pattern
!Chromosomal Pattern
!Diagnostic Significance (Yes, No or Unknown)
!Molecular Pathogenesis
!Prognostic Significance (Yes, No or Unknown)
!Prevalence -
!Therapeutic Significance (Yes, No or Unknown)
Common >20%, Recurrent 5-20% or Rare <5% (Disease)
!Notes
!Diagnostic, Prognostic, and Therapeutic Significance - D, P, T
!Established Clinical Significance Per Guidelines - Yes or No (Source)
!Clinical Relevance Details/Other Notes
|-
|-
|<span class="blue-text">EXAMPLE:</span>
|Chromosome X/Y cryptic deletion or translocation
 
|These changes cause ''CRLF2'' overexpression, upregulating the JAK-STAT pathway.
Co-deletion of 1p and 18q
|Common (>20%)
|Yes
|P
|No
|No
|Chromosome X/Y abnormalities include either translocation of the immunoglobin heavy chain enhance locus into ''CRLF2'' (''IGH''::''CRLF2''—more commonly seen in adults) or a cryptic deletion involving the PAR1 psuedoautosomal region, resulting in fusion of ''CRLF2'' and ''P2RY8'' (more commonly seen in children); these alterations involving ''CRLF2'' have been associated with poor survival;<ref name=":7">{{Cite journal|last=Konoplev|first=Sergej|last2=Lu|first2=Xinyan|last3=Konopleva|first3=Marina|last4=Jain|first4=Nitin|last5=Ouyang|first5=Juan|last6=Goswami|first6=Maitrayee|last7=Roberts|first7=Kathryn G.|last8=Valentine|first8=Marc|last9=Mullighan|first9=Charles G.|date=2017|title=CRLF2-Positive B-Cell Acute Lymphoblastic Leukemia in Adult Patients: A Single-Institution Experience|url=https://www.ncbi.nlm.nih.gov/pubmed/28340183|journal=American Journal of Clinical Pathology|volume=147|issue=4|pages=357–363|doi=10.1093/ajcp/aqx005|issn=1943-7722|pmid=28340183}}</ref> very rare alternative translocations involving ''CRLF2'' have also been observed.
|-
|Polysomy or iAMP21
|These changes stem from telomere attrition that results in amplification of all or a region of chromosome 21.
|Rare (<5%)
|P
|No
|No
|<span class="blue-text">EXAMPLE:</span>
|iAMP21 is considered high-risk cytogenetic abnormality/poor prognostic indicator, but it is not specific to B-lymphoblastic leukaemia/lymphoma with ''BCR::ABL1''-like features and can be seen in other B-lymphoblastic leukaemia/lymphomas.<ref>{{Cite journal|last=Koleilat|first=Alaa|last2=Smadbeck|first2=James B.|last3=Zepeda-Mendoza|first3=Cinthya J.|last4=Williamson|first4=Cynthia M.|last5=Pitel|first5=Beth A.|last6=Golden|first6=Crystal L.|last7=Xu|first7=Xinjie|last8=Greipp|first8=Patricia T.|last9=Ketterling|first9=Rhett P.|date=2022-12|title=Characterization of unusual iAMP21 B-lymphoblastic leukemia (iAMP21-ALL) from the Mayo Clinic and Children's Oncology Group|url=https://pubmed.ncbi.nlm.nih.gov/35771717|journal=Genes, Chromosomes & Cancer|volume=61|issue=12|pages=710–719|doi=10.1002/gcc.23084|issn=1098-2264|pmc=9549522|pmid=35771717}}</ref>
|}


See chromosomal rearrangements table as this pattern is due to an unbalanced derivative translocation associated with oligodendroglioma (add reference).
|}


<blockquote class='blockedit'>{{Box-round|title=v4:Characteristic Chromosomal Aberrations / Patterns|The content below was from the old template. Please incorporate above.}}</blockquote>
[Abnormal fluorescence ''in situ'' hybridization (FISH) results in interphase nuclei from a bone marrow sample using the ''CRLF2'' dual-color, break-apart (Cytocell) and ''IGH'' dual-color, break-apart probes, reflective of ''IGH''::''CRLF2'' rearrangement]
Approximately half of cases demonstrate rearrangements resulting in overexpression of CRLF2<ref name=":7" />. These rearrangements are the result of either translocation of immunoglobin heavy chain enhance locus into ''CRLF2'' (''IGH''-''CRLF2''—more commonly seen in adults) or through a cryptic deletion on chromosome X/Y involving the PAR1 psuedoautosomal region, resulting in fusion of ''CRLF2'' to ''P2RY8'' (more commonly seen in children). Very rare alternative translocations involving ''CRLF2'' have also been observed.
[[File:FISH 1.jpg|thumb|none]]
[[File:FISH 1.jpg|thumb|none]]


[[File:FISH 2.jpg|thumb|none]]
[[File:FISH 2.jpg|thumb|none|link=Special:FilePath/FISH_2.jpg]]
 
 
[Concurrent abnormal karyotype with trisomy 21 and a translocation involving chromosomes X, 14, and 2 in 9 of 13 cells available for analysis; metaphase FISH with the ''IGH'' break-apart probe (Vysis) confirms the presence of 5’ ''IGH'' (green signal) on the abnormal chromosome Xp33.1 (''CRLF2'' locus), highly suggestive on an ''IGH''::''CRLF2'' fusion rearrangement: 47,XX,+21c[4]/47,idem,der(X)t(X;14)(p33.1;q32),der(2)t(2;14)(p11.2;q11.2)t(X;14),der(14)t(2;14)[5]/46,XX[4].ish der(X)(5’IGH+),der(2)(3’IGH+)]


[Abnormal FISH results in interphase nuclei from a bone marrow sample using the ''CRLF2'' dual-color, break-apart (Cytocell) and ''IGH'' dual-color, break-apart probes, reflective of ''IGH''-''CRLF2'' fusion]
[[File:FISH 3.jpg|thumb|none]]
[[File:FISH 3.jpg|thumb|none]]


[[File:Karyotype.jpg|thumb|none]]
[[File:Karyotype.jpg|thumb|none]]
[Concurrent abnormal karyotype with trisomy 21 and a translocation involving chromosomes X, 14, and 2 in 9 of 13 cells available for analysis. Metaphase FISH with the ''IGH'' break-apart probe (Vysis) confirms the presence of 5’ ''IGH'' (green signal) on the abnormal chromosome Xp33.1 (''CRLF2'' locus), highly suggestive on an ''IGH''-''CRLF2'' fusion rearrangement.
47,XX,+21c[4]/47,idem,der(X)t(X;14)(p33.1;q32),der(2)t(2;14)(p11.2;q11.2)t(X;14),der(14)t(2;14)[5]/46,XX[4].ish der(X)(5’IGH+),der(2)(3’IGH+)]


(Images courtesy of Fabiola Quintero-Rivera, MD)
(Images courtesy of Fabiola Quintero-Rivera, MD)


<blockquote class="blockedit">
==Gene Mutations (SNV/INDEL)==
<center><span style="color:Maroon">'''End of V4 Section'''</span>
----
</blockquote>
==Gene Mutations (SNV / INDEL)==
 
Put your text here and fill in the table <span style="color:#0070C0">(''Instructions: This table is not meant to be an exhaustive list; please include only genes/alterations that are recurrent and common as well as either disease defining and/or clinically significant. Can include references in the table. For clinical significance, denote associations with FDA-approved therapy (not an extensive list of applicable drugs) and NCCN or other national guidelines if applicable. Can also refer to CGC workgroup tables as linked on the homepage if applicable as well as any high impact papers or reviews of gene mutations in this entity. Do not delete table.'') </span>
 
{| class="wikitable sortable"
{| class="wikitable sortable"
|-
|-
!Gene; Genetic Alteration!!'''Presumed Mechanism (Tumor Suppressor Gene [TSG] / Oncogene / Other)'''!!'''Prevalence (COSMIC /  TCGA / Other)'''!!'''Concomitant Mutations'''!!'''Mutually Exclusive Mutations'''
!Gene!!Genetic Alteration!!Tumor Suppressor Gene, Oncogene, Other!!Prevalence -
!'''Diagnostic Significance (Yes, No or Unknown)'''
Common >20%, Recurrent 5-20% or Rare <5% (Disease)
!Prognostic Significance (Yes, No or Unknown)
!Diagnostic, Prognostic, and Therapeutic Significance - D, P, T  
!Therapeutic Significance (Yes, No or Unknown)
!Established Clinical Significance Per Guidelines - Yes or No (Source)
!Notes
!Clinical Relevance Details/Other Notes
|-
|-
|<span class="blue-text">EXAMPLE:</span> TP53; Variable LOF mutations
|''CRLF2''
|[https://cancer.sanger.ac.uk/cosmic/mutation/overview?id=128002578 p.F232C]
|Oncogene
|Recurrent (5-20%)
|Unknown
|No
|p.F232C is a gain-of-function mutation that results in constitutive dimerization and cytokine independent growth within the JAK-STAT pathway.<ref>{{Cite journal|last=Yoda|first=Akinori|last2=Yoda|first2=Yuka|last3=Chiaretti|first3=Sabina|last4=Bar-Natan|first4=Michal|last5=Mani|first5=Kartik|last6=Rodig|first6=Scott J.|last7=West|first7=Nathan|last8=Xiao|first8=Yun|last9=Brown|first9=Jennifer R.|date=2010-01-05|title=Functional screening identifies CRLF2 in precursor B-cell acute lymphoblastic leukemia|url=https://pubmed.ncbi.nlm.nih.gov/20018760|journal=Proceedings of the National Academy of Sciences of the United States of America|volume=107|issue=1|pages=252–257|doi=10.1073/pnas.0911726107|issn=1091-6490|pmc=2806782|pmid=20018760}}</ref>
|-
|''JAK1''
''JAK2''
|[https://cancer.sanger.ac.uk/cosmic/mutation/overview?id=109242705 p.V658F][https://cancer.sanger.ac.uk/cosmic/mutation/overview?id=123403459 p.R683G]
|Oncogene
|Recurrent (5-20%)
|Unknown
|No
|Half of cases with ''CRLF2'' overexpression have activating mutations in ''JAK1'' or ''JAK2'' that promote downstream JAK-STAT signaling;<ref name=":10" /> the  most common mutation, p.R683G, occurs in the pseudokinase domain of ''JAK2'', and less common ''JAK1'' alterations have been detected, which include p.V658F most frequently; clinical trials examining the treatment effects of targeting JAK proteins are currently ongoing.<ref>{{Cite journal|last=Goulart|first=Hannah|last2=Jabbour|first2=Elias|last3=Short|first3=Nicholas J.|last4=Kadia|first4=Tapan M.|last5=Pemmaraju|first5=Naveen|last6=Takahashi|first6=Koichi|last7=Ravandi|first7=Farhad|last8=Konopleva|first8=Marina|last9=Jain|first9=Nitin|date=2025-11|title=A Phase I/II Trial of Ruxolitinib with Chemotherapy for Patients with Relapsed and/or Refractory Philadelphia-like Acute Lymphoblastic Leukemia|url=https://pubmed.ncbi.nlm.nih.gov/40500616|journal=Clinical Lymphoma, Myeloma & Leukemia|volume=25|issue=11|pages=800–807|doi=10.1016/j.clml.2025.05.013|issn=2152-2669|pmid=40500616}}</ref>
|-
|''IL7R''
|Activating mutations
|Oncogene
|Recurrent (5-20%)
|Unknown
|No
|''IL7R'' is the partner gene of ''CRLF2''; gain-of-function mutations potentiate CRFL2 and its cofactor IL7RA forming a receptor for thymic stromal-derived lymphopoietin, leading to JAK-STAT activation.<ref name=":8">Quesada A, Reynolds M, Jorgensen JL, et al. Cytokine receptor-like factor 2 (CRLF2) expression in precursor B-lymphoblastic leukemia. International Clinical Cytometry Society e-Newsletter. 2014;5(1).</ref>
|-
|''SH2B3''
''IL2RB''


<span class="blue-text">EXAMPLE:</span>
''TYK2''


EGFR; Exon 20 mutations
''TLSP''
 
|Activating mutations
<span class="blue-text">EXAMPLE:</span> BRAF; Activating mutations
|Oncogene
|<span class="blue-text">EXAMPLE:</span> TSG
|Recurrent (5-20%)
|<span class="blue-text">EXAMPLE:</span> 20% (COSMIC)
|Unknown
 
|No
<span class="blue-text">EXAMPLE:</span> 30% (add Reference)
|These result in constitutive activation of JAK-STAT signaling and are often present as multi-subclonal (suggestive of secondary driver events).<ref>{{Cite journal|last=Jain|first=Sarika|last2=Abraham|first2=Anu|date=2020-02|title=BCR-ABL1-like B-Acute Lymphoblastic Leukemia/Lymphoma: A Comprehensive Review|url=https://pubmed.ncbi.nlm.nih.gov/31644323|journal=Archives of Pathology & Laboratory Medicine|volume=144|issue=2|pages=150–155|doi=10.5858/arpa.2019-0194-RA|issn=1543-2165|pmid=31644323}}</ref>
|<span class="blue-text">EXAMPLE:</span> IDH1 R123H
|-
|<span class="blue-text">EXAMPLE:</span> EGFR amplification
|''RAS'' pathway genes
|
|Activating mutations
|
|Oncogenes
|
|Recurrent (5-20%)
|<span class="blue-text">EXAMPLE:</span>  Excludes hairy cell leukemia (HCL) (add reference).
|Unknown
<br />
|No
|}
|Activating mutations in ''KRAS'', ''NF1'', ''PTPN11'', and other genes upregulate the MAP kinase pathway and have been found at a higher frequency in B-lymphoblastic  leukaemia/lymphoma with ''BCR::ABL1''-like features compared to other B-lymphoblastic leukaemia/lymphomas.<ref>{{Cite journal|last=Lee|first=Jae Wook|last2=Kim|first2=Yonggoo|last3=Cho|first3=Bin|last4=Kim|first4=Seongkoo|last5=Jang|first5=Pil-Sang|last6=Lee|first6=Jaewoong|last7=Cho|first7=Hanwool|last8=Lee|first8=Gun Dong|last9=Chung|first9=Nack-Gyun|date=2020-07|title=High incidence of RAS pathway mutations among sentinel genetic lesions of Korean pediatric BCR-ABL1-like acute lymphoblastic leukemia|url=https://pubmed.ncbi.nlm.nih.gov/32378810|journal=Cancer Medicine|volume=9|issue=13|pages=4632–4639|doi=10.1002/cam4.3099|issn=2045-7634|pmc=7333828|pmid=32378810}}</ref>
Note: A more extensive list of mutations can be found in cBioportal (https://www.cbioportal.org/), COSMIC (https://cancer.sanger.ac.uk/cosmic), ICGC (https://dcc.icgc.org/) and/or other databases. When applicable, gene-specific pages within the CCGA site directly link to pertinent external content.
|}Note: A more extensive list of mutations can be found in [https://www.cbioportal.org/ <u>cBioportal</u>], [https://cancer.sanger.ac.uk/cosmic <u>COSMIC</u>], and/or other databases. When applicable, gene-specific pages within the CCGA site directly link to pertinent external content
 
 
<blockquote class='blockedit'>{{Box-round|title=v4:Gene Mutations (SNV/INDEL)|The content below was from the old template. Please incorporate above.}}</blockquote>
In addition to gene translocations, gain-of-function mutations in ''CRLF2'' itself or in its partner gene, ''IL7RA'', have been seen<ref name=":8">Quesada A, Reynolds M, Jorgensen JL, et al. Cytokine receptor-like factor 2 (CRLF2) expression in precursor B-lymphoblastic leukemia. International Clinical Cytometry Society e-Newsletter. 2014;5(1).</ref>.  Alternative alterations activating kinase signaling occur, including activating mutations of ''FLT3'', as well as focal deletions of ''SH2B3'' (also known as ''LNK'')<ref>Tosi S & Reid AG. The Genetic Basis of Haematological Cancers. John Wiley & Sons, Incorporated: Chichester, United Kingdom: 2016.</ref>.
 
Herold et al. in 2017 reported a wide variety of molecular alterations in BCR-ABL1-like B-ALL, which was shown to have statistically significant associations with alterations of ''IKZF1'', ''CRLF2'', ''JAK2'', ''BTG1'', and high ''CRLF2'' expression<ref name=":5" />.
 
<blockquote class="blockedit">
<center><span style="color:Maroon">'''End of V4 Section'''</span>
----
</blockquote>
==Epigenomic Alterations==
==Epigenomic Alterations==
Not applicable
Not applicable
Line 304: Line 701:
==Genes and Main Pathways Involved==
==Genes and Main Pathways Involved==


Put your text here and fill in the table <span style="color:#0070C0">(''Instructions: Can include references in the table. Do not delete table.'')</span>
{| class="wikitable sortable"
{| class="wikitable sortable"
|-
|-
!Gene; Genetic Alteration!!Pathway!!Pathophysiologic Outcome
!Gene; Genetic Alteration!!Pathway!!Pathophysiologic Outcome
|-
|-
|<span class="blue-text">EXAMPLE:</span> BRAF and MAP2K1; Activating mutations
|ABL-class rearrangements
|<span class="blue-text">EXAMPLE:</span> MAPK signaling
|Tyrosine kinase signaling
|<span class="blue-text">EXAMPLE:</span> Increased cell growth and proliferation
|These result in B-cell progenitor proliferation; may be responsive to TKIs.<ref>{{Cite journal|last=Senapati|first=Jayastu|last2=Jabbour|first2=Elias|last3=Konopleva|first3=Marina|last4=Short|first4=Nicholas J.|last5=Tang|first5=Guilin|last6=Daver|first6=Naval|last7=Kebriaei|first7=Partow|last8=Kadia|first8=Tapan|last9=Pemmaraju|first9=Naveen|date=2023-05|title=Philadelphia-Like Genetic Rearrangements in Adults With B-Cell ALL: Refractoriness to Chemotherapy and Response to Tyrosine Kinase Inhibitor in ABL Class Rearrangements|url=https://pubmed.ncbi.nlm.nih.gov/37196217|journal=JCO precision oncology|volume=7|pages=e2200707|doi=10.1200/PO.22.00707|issn=2473-4284|pmc=10309573|pmid=37196217}}</ref>
|-
|-
|<span class="blue-text">EXAMPLE:</span> CDKN2A; Inactivating mutations
|''CRLF2'' overexpression; mutations of ''CRLF2'', ''JAK1/2'', ''IL7R, SH2B3, IL2RB, TYK2,'' and ''TLSP''; ''JAK2'' and ''EPOR'' rearrangements
|<span class="blue-text">EXAMPLE:</span> Cell cycle regulation
|JAK-STAT signaling
|<span class="blue-text">EXAMPLE:</span> Unregulated cell division
|These potentiate the JAK2-signal transducer and upregulate the transcription 5 pathway;<ref name=":8" /> other mutations not in ''CRLF2'' and ''IL7R'' cause constitutive JAK/STAT activation downstream of CRLF2.
|-
|-
|<span class="blue-text">EXAMPLE:</span>  KMT2C and ARID1A; Inactivating mutations
|''IKZF1'' deletion
|<span class="blue-text">EXAMPLE:</span>  Histone modification, chromatin remodeling
|IKAROS transcription factor signaling
|<span class="blue-text">EXAMPLE:</span>  Abnormal gene expression program
|This results in activation of ''EBF1'', ''MSH2'', and ''MCL1'', leading to B-cell leukemogenesis.<ref>{{Cite journal|last=van der Veer|first=Arian|last2=Waanders|first2=Esmé|last3=Pieters|first3=Rob|last4=Willemse|first4=Marieke E.|last5=Van Reijmersdal|first5=Simon V.|last6=Russell|first6=Lisa J.|last7=Harrison|first7=Christine J.|last8=Evans|first8=William E.|last9=van der Velden|first9=Vincent H. J.|date=2013|title=Independent prognostic value of BCR-ABL1-like signature and IKZF1 deletion, but not high CRLF2 expression, in children with B-cell precursor ALL|url=https://www.ncbi.nlm.nih.gov/pubmed/23974192|journal=Blood|volume=122|issue=15|pages=2622–2629|doi=10.1182/blood-2012-10-462358|issn=1528-0020|pmc=3795461|pmid=23974192}}</ref>
|}
|}


<blockquote class='blockedit'>{{Box-round|title=v4:Genes and Main Pathways Involved|The content below was from the old template. Please incorporate above.}}</blockquote>
*IKAROS transcription factor:  Deletion of ''IKZF1'' results in activation of ''EBF1'', ''MSH2'', and ''MCL1'', leading to B-cell leukemogenesis<ref>{{Cite journal|last=van der Veer|first=Arian|last2=Waanders|first2=Esmé|last3=Pieters|first3=Rob|last4=Willemse|first4=Marieke E.|last5=Van Reijmersdal|first5=Simon V.|last6=Russell|first6=Lisa J.|last7=Harrison|first7=Christine J.|last8=Evans|first8=William E.|last9=van der Velden|first9=Vincent H. J.|date=2013|title=Independent prognostic value of BCR-ABL1-like signature and IKZF1 deletion, but not high CRLF2 expression, in children with B-cell precursor ALL|url=https://www.ncbi.nlm.nih.gov/pubmed/23974192|journal=Blood|volume=122|issue=15|pages=2622–2629|doi=10.1182/blood-2012-10-462358|issn=1528-0020|pmc=3795461|pmid=23974192}}</ref>.
*''CRLF2'' overexpression:  CRFL2 and its cofactor IL7RA form a receptor for thymic stromal-derived lymphopoietin that activates the JAK2-signal transducer and upregulates the transcription 5 pathway<ref name=":8" />.
*Dysregulation of several tyrosine kinase signaling pathways (involving ''ABL1'', ''ABL2'', ''PDGFRB'', ''CSF1'', etc.) results in B-cell progenitor proliferation.
<blockquote class="blockedit">
<center><span style="color:Maroon">'''End of V4 Section'''</span>
----
</blockquote>
==Genetic Diagnostic Testing Methods==
==Genetic Diagnostic Testing Methods==


*Flow cytometry for ''CRLF2'' has been shown in some studies to be 100% concordant with FISH results<ref name=":7" />.
*Flow cytometry for ''CRLF2'' has been shown in some studies to be 100% concordant with FISH results<ref name=":7" />.
*Next-generation sequencing is helpful for detecting copy number changes, single nucleotide variants, and gene fusions involving ''CRLF2'', ''ABL1'', ''ABL2'', ''JAK2'', etc.
*Next-generation sequencing is helpful for detecting copy number changes, single nucleotide variants, and gene fusions involving ''CRLF2'', ''ABL1'', ''ABL2'', ''JAK2'', etc.
*Gene expression profile algorithms, incorporating prediction analysis or hierarchical clustering of microarrays, provide the definitive diagnosis of BCR-ABL1-like B-ALL.
*Gene expression profile algorithms, incorporating prediction analysis or hierarchical clustering of microarrays, provide a definitive diagnosis of B-lymphoblastic leukaemia/lymphoma with ''BCR::ABL1''-like features.


==Familial Forms==
==Familial Forms==
Families with certain inherited variants of ''GATA3'' (often seen in Native-American populations) are at increased risk of BCR-ABL1-like B-ALL<ref>{{Cite journal|last=Perez-Andreu|first=Virginia|last2=Roberts|first2=Kathryn G.|last3=Harvey|first3=Richard C.|last4=Yang|first4=Wenjian|last5=Cheng|first5=Cheng|last6=Pei|first6=Deqing|last7=Xu|first7=Heng|last8=Gastier-Foster|first8=Julie|last9=E|first9=Shuyu|date=2013|title=Inherited GATA3 variants are associated with Ph-like childhood acute lymphoblastic leukemia and risk of relapse|url=https://www.ncbi.nlm.nih.gov/pubmed/24141364|journal=Nature Genetics|volume=45|issue=12|pages=1494–1498|doi=10.1038/ng.2803|issn=1546-1718|pmc=4039076|pmid=24141364}}</ref>.
Families with certain inherited variants of ''GATA3'' (often seen in Native-American populations) are at increased risk of B-lymphoblastic leukaemia/lymphoma with ''BCR::ABL1''-like features.<ref>{{Cite journal|last=Perez-Andreu|first=Virginia|last2=Roberts|first2=Kathryn G.|last3=Harvey|first3=Richard C.|last4=Yang|first4=Wenjian|last5=Cheng|first5=Cheng|last6=Pei|first6=Deqing|last7=Xu|first7=Heng|last8=Gastier-Foster|first8=Julie|last9=E|first9=Shuyu|date=2013|title=Inherited GATA3 variants are associated with Ph-like childhood acute lymphoblastic leukemia and risk of relapse|url=https://www.ncbi.nlm.nih.gov/pubmed/24141364|journal=Nature Genetics|volume=45|issue=12|pages=1494–1498|doi=10.1038/ng.2803|issn=1546-1718|pmc=4039076|pmid=24141364}}</ref>  


==Additional Information==
==Additional Information==


Put your text here
Clinical trial of TKI in B-lymphoblastic leukaemia/lymphoma with ''BCR::ABL1''-like features (Clinicaltrials.gov Identifier: [https://www.clinicaltrials.gov/study/NCT02883049 NCT02883049])
 
Clinical trial of JAK inhibitor in B-lymphoblastic leukaemia/lymphoma with ''BCR::ABL1''-like features (Clinicaltrials.gov Identifier: [https://clinicaltrials.gov/study/NCT02723994 NCT02723994])


==Links==
==Links==
Line 358: Line 746:
[[IKZF1]]  
[[IKZF1]]  


Pre-B ALL B-lymphoblastic leukemia/lymphoma with ''BCR-ABL1''-like/Ph-like in Pathology Outlines (http://www.pathologyoutlines.com/topic/leukemiaprebbcrabl1like.html)
B-lymphoblastic leukaemia/lymphoma with ''BCR::ABL1''-like features in [https://www.pathologyoutlines.com/topic/leukemiaprebbcrabl1like.html Pathology Outlines]


==References==
==References==
(use the "Cite" icon at the top of the page) <span style="color:#0070C0">(''Instructions: Add each reference into the text above by clicking on where you want to insert the reference, selecting the “Cite” icon at the top of the page, and using the “Automatic” tab option to search such as by PMID to select the reference to insert. The reference list in this section will be automatically generated and sorted.''</span> <span style="color:#0070C0">''If a PMID is not available, such as for a book, please use the “Cite” icon, select “Manual” and then “Basic Form”, and include the entire reference''</span><span style="color:#0070C0">''.''</span><span style="color:#0070C0">) </span> <references />
(use the "Cite" icon at the top of the page) <span style="color:#0070C0">(''Instructions: Add each reference into the text above by clicking where you want to insert the reference, selecting the “Cite” icon at the top of the wiki page, and using the “Automatic” tab option to search by PMID to select the reference to insert. If a PMID is not available, such as for a book, please use the “Cite” icon, select “Manual” and then “Basic Form”, and include the entire reference. To insert the same reference again later in the page, select the “Cite” icon and “Re-use” to find the reference; DO NOT insert the same reference twice using the “Automatic” tab as it will be treated as two separate references. The reference list in this section will be automatically generated and sorted''</span><span style="color:#0070C0">''.''</span><span style="color:#0070C0">)</span> <references />


'''
==Notes==
<nowiki>*</nowiki>Primary authors will typically be those that initially create and complete the content of a page.  If a subsequent user modifies the content and feels the effort put forth is of high enough significance to warrant listing in the authorship section, please contact the [[Leadership|''<u>Associate Editor</u>'']] or other CCGA representative.  When pages have a major update, the new author will be acknowledged at the beginning of the page, and those who contributed previously will be acknowledged below as a prior author.


==Notes==
Prior Author(s):  Fabiola Quintero-Rivera, MD 
<nowiki>*</nowiki>Primary authors will typically be those that initially create and complete the content of a page.  If a subsequent user modifies the content and feels the effort put forth is of high enough significance to warrant listing in the authorship section, please contact the CCGA coordinators (contact information provided on the homepage).  Additional global feedback or concerns are also welcome.
       
<nowiki>*</nowiki>''Citation of this Page'': “B-lymphoblastic leukaemia/lymphoma with BCR::ABL1-like features”. Compendium of Cancer Genome Aberrations (CCGA), Cancer Genomics Consortium (CGC), updated {{REVISIONMONTH}}/{{REVISIONDAY}}/{{REVISIONYEAR}}, <nowiki>https://ccga.io/index.php/HAEM5:B-lymphoblastic_leukaemia/lymphoma_with_BCR::ABL1-like_features</nowiki>.
<nowiki>*</nowiki>''Citation of this Page'': “B-lymphoblastic leukaemia/lymphoma with BCR::ABL1-like features”. Compendium of Cancer Genome Aberrations (CCGA), Cancer Genomics Consortium (CGC), updated {{REVISIONMONTH}}/{{REVISIONDAY}}/{{REVISIONYEAR}}, <nowiki>https://ccga.io/index.php/HAEM5:B-lymphoblastic_leukaemia/lymphoma_with_BCR::ABL1-like_features</nowiki>.
[[Category:HAEM5]][[Category:DISEASE]][[Category:Diseases B]]
[[Category:HAEM5]]
[[Category:DISEASE]]
[[Category:Diseases B]]

Latest revision as of 16:08, 6 November 2025


Haematolymphoid Tumours (WHO Classification, 5th ed.)

editContent Update To WHO 5th Edition Classification Is In Process; Content Below is Based on WHO 4th Edition Classification
This page was converted to the new template on 2023-12-07. The original page can be found at HAEM4:B-Lymphoblastic Leukemia/Lymphoma, BCR-ABL1-Like.

(General Instructions – The focus of these pages is the clinically significant genetic alterations in each disease type. This is based on up-to-date knowledge from multiple resources such as PubMed and the WHO classification books. The CCGA is meant to be a supplemental resource to the WHO classification books; the CCGA captures in a continually updated wiki-stye manner the current genetics/genomics knowledge of each disease, which evolves more rapidly than books can be revised and published. If the same disease is described in multiple WHO classification books, the genetics-related information for that disease will be consolidated into a single main page that has this template (other pages would only contain a link to this main page). Use HUGO-approved gene names and symbols (italicized when appropriate), HGVS-based nomenclature for variants, as well as generic names of drugs and testing platforms or assays if applicable. Please complete tables whenever possible and do not delete them (add N/A if not applicable in the table and delete the examples); to add (or move) a row or column in a table, click nearby within the table and select the > symbol that appears. Please do not delete or alter the section headings. The use of bullet points alongside short blocks of text rather than only large paragraphs is encouraged. Additional instructions below in italicized blue text should not be included in the final page content. Please also see Author_Instructions and FAQs as well as contact your Associate Editor or Technical Support.)

Primary Author(s)*

Mark G. Evans, MD, Caris Life Sciences

Sumire K. Kitahara, MD, Cedars-Sinai Medical Center

WHO Classification of Disease

Structure Disease
Book Haematolymphoid Tumours (5th ed.)
Category B-cell lymphoid proliferations and lymphomas
Family Precursor B-cell neoplasms
Type B-lymphoblastic leukaemias/lymphomas
Subtype(s) B-lymphoblastic leukaemia/lymphoma with BCR::ABL1-like features

Related Terminology

Acceptable Philadelphia-like (Ph-like) B-ALL; BCR::ABL1-like B-ALL/LBL
Not Recommended N/A

Gene Rearrangements

B-lymphoblastic leukaemia/lymphoma with BCR::ABL1-like features traditionally required diagnosis by gene expression (GEX) profiling[1][2] and was found to exhibit a GEX profile similar to Philadelphia chromosome-positive B-lymphoblastic leukaemia/lymphoma but lacking BCR::ABL1. The WHO[3] and ICC[4] have since recognized recurring genomic alterations associated with B-lymphoblastic leukaemia/lymphoma with BCR::ABL1-like features, including ABL-class rearrangements, JAK-STAT activating alterations, and others. Proper identification of this disease is important, as patients may respond to targeted therapies like tyrosine kinase inhibitors (TKIs);[5] however, as most reports feature only single cases and limited series, consensus on the diagnostic/prognostic/therapeutic significance of the various genomic alterations has not been reached and currently being established.


Table derived from Akkari et al., 2020 [6] with permission from Cancer Genetics summarizes the important gene rearrangements associated with B-lymphoblastic leukaemia/lymphoma with BCR::ABL1-like features.

3’ Partner 5’ Partner Chromosome rearrangement Gene fusion Visible by G-banding References Comment
ABL1

(9q34)

CENPC1 t(4;9)(q13;q34) CENPC1::ABL1 YES [7] Requires complex rearrangement due to incompatible orientation of genes with respect to chromosome arms
ETV6 t(9;12)(q34;p13) ETV6::ABL1 NO [8] Requires complex rearrangement due to incompatible orientation of genes with respect to chromosome arms
FOXP1 t(3;9)(p13;q34) FOXP1::ABL1 on der(3) YES [9]
LSM14A t(9;19)(q34;q13.1) LSM14A::ABL1 on der(19) YES [7]
NUP153 t(6;9)(p22.3;q34) NUP153::ABL1 on der(6) YES [7]
NUP214 dup(9)(q34.1q34.1) NUP214::ABL1 NO [10] Tandem duplication (~370 kb) detectable by CMA
RANBP2 t(2;9)(q12.3;q34) RANBP::ABL1 on der(2) YES [5]
RCSD1 t(1;9)(q24.2;q34) RCSD1::ABL1 on der(1) YES [11]
SFPQ t(1;9)(p34.3;q34) SFPQ::ABL1 on der(1) YES [12]
SNX1 t(9;15)(q34;q22.3) SNX1::ABL1 on der(15) YES [13]
SNX2 t(5;9)(q23.2;q34) SNX2::ABL1 on der(5) YES [14]
ZMIZ1 t(9;10)(q34;q22.3) ZMIZ1::ABL1 on der(10) YES [15]
ABL2

(1q25.2)

PAG1 t(1;8)(q25.2;q21.1) PAG1::ABL2 on der(1) YES [5]
RCSD1 1q24.2q25.2 rearrangement RCSD1::ABL2 NO [16] On the same chromosome arm; however, a simple deletion cannot cause the fusion due to the orientation of genes
ZC3HAV1 t(1;7)(q25.2;q34) ZC3HAV1::ABL2 on der(1) YES [17]
CRLF2

(Xp22.3 & Yp11.3)

IGH t(X;14)(p22.3;q32) or

t(Y;14)(p11.3;q32)

IGH::CRLF2 NO [18][5]
P2RY8 del(X)(p22.3p22.3) or del(Y)(p11.3p11.3) P2RY8::CRLF2 NO [18][5]
CSF1R

(5q32)

MEF2D t(1;5)(q22;q32) MEF2D::CSF1R on der(5) YES [19]
SSBP2 5q14.1q32 rearrangement SSBP2::CSF1R YES [7] On the same chromosome arm; however, a simple deletion cannot cause the fusion due to the orientation of genes
TBL1XR1 t(3;5)(q26.3;q32) TBL1XR1::CSF1R on der(5) YES [7]
DGKH (13q14.1) ZFAND3 t(6;13)(p21.2;q14.1) ZFAND3::DGKH YES [5] Requires complex rearrangement due to incompatible orientation of genes with respect to chromosome arms
EPOR (19p13.2) IGH ins(14;19)(q32;p13.2p13.2) IGH/EPOR Cryptic insertion [20]
IGK ins(2;19)(p11.2;p13.2p13.2) IGK/EPOR Cryptic insertion [20]
LAIR1 inv(19)(p13.2q13.42) LAIR1::EPOR NO [20] Inversion of chromosome 19 juxtaposes EPOR to the upstream region of LAIR1
THADA t(2;19)(p21;p13.2) THADA::EPOR YES [13]
IL2RB (22q12.3) MYH9 22q12.3 rearrangement MYH9::IL2RB NO [5] On the same chromosome arm; however, a simple deletion cannot cause the fusion due to the orientation of genes
JAK2

(9p24.1)

ATF7IP t(9;12)(p24.1;p13.1) ATF7IP::JAK2 on der(9) NO [5][21]
BCR t(9;22)(p24.1;q11.2) BCR::JAK2 ? YES [22] Seen also in myeloproliferative neoplasms. Requires complex rearrangement due to incompatible orientation of genes with respect to chromosome arms
EBF1 t(5;9)(q33.3;p24.1) EBF1::JAK2 on der(9) NO (SUBTLE) [23]
ETV6 t(9;12)(p24.1;p13.2) ETV6::JAK2 on der(9) NO (SUBTLE) [24][25]
GOLGA5 t(9;14)(p24.1;q32.1) GOLGA5::JAK2 NO (SUBTLE) [26] Requires complex rearrangement due to incompatible orientation of genes with respect to chromosome arms
HMBOX1 t(8;9)(p21.1;p24.1) HMBOX1::JAK2 on der(9) YES [27]
OFD1 t(X;9)(p22.2;p24.1) OFD1::JAK2 on der(9) NO (SUBTLE) [28]
PAX5 inv(9)(p13.2p24.1) PAX5::JAK2 YES [29] An inversion is required as genes are oriented in opposite directions
PCM1 t(8;9)(p22;p24.1) PCM1::JAK2 on der(9) YES (SUBTLE) [13] Seen also in myeloid/lymphoid neoplasms with eosinophilia
PPFIBP1 t(9;12)(p24.1;p11.2) PPFIBP1::JAK2 on der(9) YES [13]
RFX3 inv(9)(p24.1p24.2) RFX3::JAK2 NO [7] An inversion is required as genes are oriented in opposite directions
SMU1 inv(9)(p21.1p24.1) SMU1::JAK2 NO [27] An inversion is required as genes are oriented in opposite directions
SNX29 t(9;16)(p24.1;p13.1) SNX29::JAK2 on der(9) YES [27]
SPAG9 t(9;17)(p24.1;q21.3) SPAG9::JAK2 on der(9) YES [30]
SSBP2 t(5;9)(q14.1;p24.1) SSBP2::JAK2 on der(9) YES [31]
STRN3 t(9;14)(p24.1;q12) STRN3::JAK2 on der(9) YES [32]
TERF2 t(9;16)(p24.1;q22.1) TERF2::JAK2 on der(9) YES [33]
TPR t(1;9)(q31.1;p24.1) TPR::JAK2 on der(9) YES [5]
USP25 t(9;21)(p24.1;q21.1) USP25::JAK2 ? YES [7] Requires complex rearrangement due to incompatible orientation of genes with respect to chromosome arms
ZBTB46 t(9;20)(p24.1;q13.3) ZBTB46::JAK2 on der(9) NO [13]
ZNF274 t(9;19)(p24.1;q13.4) ZNF274::JAK2 NO [7] Requires complex rearrangement due to incompatible orientation of genes with respect to chromosome arms
ZNF340 t(9;20)(p24.1;q13.3) ZNF340::JAK2 on der(9) NO [13]
PDGFRA

(4q12)

FIP1L1 del(4)(q12q12) FIP1L1::PDGFRA NO [27] Interstitial deletion. Seen also in myeloid/lymphoid neoplasms with eosinophilia
PDGFRB (5q32) ATF7IP t(5;12)(q32;p13.1) ATF7IP::PDGFRB on der(5) YES [34][35][36]
EBF1 del(5)(q32q33.3) EBF1::PDGFRB NO [37] Interstitial deletion
ETV6 t(5;12)(q32;p13.2) ETV6::PDGFRB on der(5) YES [13]
SNX29 t(5;16)(q32;p13.1) SNX29::PDGFRB on der(5) YES [13]
SSBP2 t(5;5)(q14.1;q32) SSBP2::PDGFRB ? YES [13] On the same chromosome arm; however, a simple deletion cannot cause the fusion due to the orientation of genes
TNIP1 del(5)(q32q33.1) TNIP1::PDGFRB NO [13] Interstitial deletion. Seen also in myeloid/lymphoid neoplasms with eosinophilia
ZEB2 t(2;5)(q22.3;q32) ZEB2::PDGFRB on der(5) YES [5]
ZMYND8 t(5;20)(q32;q13.1) ZMYND8::PDGFRB on der(5) YES [7]
PTK2B (8p21.2) KDM6A t(X;8)(p11.3;p21.2) KDM6A::PTK2B on der(8) YES [5]
STAG2 t(X;8)(q25;p21.2) STAG2::PTK2B YES [5] Requires complex rearrangement due to incompatible orientation of genes with respect to chromosome arms
TMEM2 t(8;9)(p21.2;q21.1) TMEM2::PTK2B on der(8) YES [13]
TYK2 (19p13.2) MYB t(6;19)(q23.3;p13.2) MYB::TYK2 on der(6) YES [23]
SMARCA4 inv(19)(p13.2p13.2) SMARCA4::TYK2 NO [13]
ZNF340 t(19;20)(p13.2;q13.3) ZNF340::TYK2 NO [13] Requires complex rearrangement due to incompatible orientation of genes with respect to chromosome arms

Individual Region Genomic Gain/Loss/LOH

Chr # Gain, Loss, Amp, LOH Minimal Region Cytoband and/or Genomic Coordinates [Genome Build; Size] Relevant Gene(s) Diagnostic, Prognostic, and Therapeutic Significance - D, P, T Established Clinical Significance Per Guidelines - Yes or No (Source) Clinical Relevance Details/Other Notes
5 Loss chr5:158,695,920-159,099,916

[GRCh38/hg38]

EBF1 Unknown No Deletion of EBF1 results in altered B-cell development.[38]
7 Loss chr7:50,303,455-50,405,101

[GRCh38/hg38]

IKZF1 P Yes, NCCN - Acute Lymphoblastic leukaemia Monoallelic (often partial) deletion of the IKAROS transcription factor, encoded by IKZF1, is one of the most frequently observed genetic abnormalities in B-lymphoblastic leukaemia/lymphoma with BCR::ABL1-like features, although this finding is not specific and not included in the definition;[39] IKZF1 deletion is associated with poor prognosis.[40]
9 Loss chr9:21,967,752-21,995,324

chr9:22,002,903-22,009,313

[GRCh38/hg38]

CDKN2A

CDKN2B

Unknown No Deletion of CDKN2A/B results in altered B-cell development.[38]
9 Loss chr9:36,833,269-37,034,268

[GRCh38/hg38]

PAX5 Unknown No Deletion of PAX5 results in altered B-cell development.[38]
12 Loss chr12:11,649,674-11,895,377

[GRCh38/hg38]

ETV6 Unknown No Deletion of ETV6 results in altered B-cell development.[38]
13 Loss chr13:48,303,744-48,599,436

[GRCh38/hg38]

RB1 Unknown No Deletion of RB1 results in disrupted cell-cycle regulation.[38]
17 Loss chr17:7,661,779-7,687,546

[GRCh38/hg38]

TP53 Unknown No Deletion of TP53 results in in disrupted cell-cycle regulation.[38]

Characteristic Chromosomal or Other Global Mutational Patterns

Chromosomal Pattern Molecular Pathogenesis Prevalence -

Common >20%, Recurrent 5-20% or Rare <5% (Disease)

Diagnostic, Prognostic, and Therapeutic Significance - D, P, T Established Clinical Significance Per Guidelines - Yes or No (Source) Clinical Relevance Details/Other Notes
Chromosome X/Y cryptic deletion or translocation These changes cause CRLF2 overexpression, upregulating the JAK-STAT pathway. Common (>20%) P No Chromosome X/Y abnormalities include either translocation of the immunoglobin heavy chain enhance locus into CRLF2 (IGH::CRLF2—more commonly seen in adults) or a cryptic deletion involving the PAR1 psuedoautosomal region, resulting in fusion of CRLF2 and P2RY8 (more commonly seen in children); these alterations involving CRLF2 have been associated with poor survival;[41] very rare alternative translocations involving CRLF2 have also been observed.
Polysomy or iAMP21 These changes stem from telomere attrition that results in amplification of all or a region of chromosome 21. Rare (<5%) P No iAMP21 is considered high-risk cytogenetic abnormality/poor prognostic indicator, but it is not specific to B-lymphoblastic leukaemia/lymphoma with BCR::ABL1-like features and can be seen in other B-lymphoblastic leukaemia/lymphomas.[42]


[Abnormal fluorescence in situ hybridization (FISH) results in interphase nuclei from a bone marrow sample using the CRLF2 dual-color, break-apart (Cytocell) and IGH dual-color, break-apart probes, reflective of IGH::CRLF2 rearrangement]


[Concurrent abnormal karyotype with trisomy 21 and a translocation involving chromosomes X, 14, and 2 in 9 of 13 cells available for analysis; metaphase FISH with the IGH break-apart probe (Vysis) confirms the presence of 5’ IGH (green signal) on the abnormal chromosome Xp33.1 (CRLF2 locus), highly suggestive on an IGH::CRLF2 fusion rearrangement: 47,XX,+21c[4]/47,idem,der(X)t(X;14)(p33.1;q32),der(2)t(2;14)(p11.2;q11.2)t(X;14),der(14)t(2;14)[5]/46,XX[4].ish der(X)(5’IGH+),der(2)(3’IGH+)]

(Images courtesy of Fabiola Quintero-Rivera, MD)

Gene Mutations (SNV/INDEL)

Gene Genetic Alteration Tumor Suppressor Gene, Oncogene, Other Prevalence -

Common >20%, Recurrent 5-20% or Rare <5% (Disease)

Diagnostic, Prognostic, and Therapeutic Significance - D, P, T   Established Clinical Significance Per Guidelines - Yes or No (Source) Clinical Relevance Details/Other Notes
CRLF2 p.F232C Oncogene Recurrent (5-20%) Unknown No p.F232C is a gain-of-function mutation that results in constitutive dimerization and cytokine independent growth within the JAK-STAT pathway.[43]
JAK1

JAK2

p.V658Fp.R683G Oncogene Recurrent (5-20%) Unknown No Half of cases with CRLF2 overexpression have activating mutations in JAK1 or JAK2 that promote downstream JAK-STAT signaling;[13] the most common mutation, p.R683G, occurs in the pseudokinase domain of JAK2, and less common JAK1 alterations have been detected, which include p.V658F most frequently; clinical trials examining the treatment effects of targeting JAK proteins are currently ongoing.[44]
IL7R Activating mutations Oncogene Recurrent (5-20%) Unknown No IL7R is the partner gene of CRLF2; gain-of-function mutations potentiate CRFL2 and its cofactor IL7RA forming a receptor for thymic stromal-derived lymphopoietin, leading to JAK-STAT activation.[45]
SH2B3

IL2RB

TYK2

TLSP

Activating mutations Oncogene Recurrent (5-20%) Unknown No These result in constitutive activation of JAK-STAT signaling and are often present as multi-subclonal (suggestive of secondary driver events).[46]
RAS pathway genes Activating mutations Oncogenes Recurrent (5-20%) Unknown No Activating mutations in KRAS, NF1, PTPN11, and other genes upregulate the MAP kinase pathway and have been found at a higher frequency in B-lymphoblastic leukaemia/lymphoma with BCR::ABL1-like features compared to other B-lymphoblastic leukaemia/lymphomas.[47]

Note: A more extensive list of mutations can be found in cBioportal, COSMIC, and/or other databases. When applicable, gene-specific pages within the CCGA site directly link to pertinent external content

Epigenomic Alterations

Not applicable

Genes and Main Pathways Involved

Gene; Genetic Alteration Pathway Pathophysiologic Outcome
ABL-class rearrangements Tyrosine kinase signaling These result in B-cell progenitor proliferation; may be responsive to TKIs.[48]
CRLF2 overexpression; mutations of CRLF2, JAK1/2, IL7R, SH2B3, IL2RB, TYK2, and TLSP; JAK2 and EPOR rearrangements JAK-STAT signaling These potentiate the JAK2-signal transducer and upregulate the transcription 5 pathway;[45] other mutations not in CRLF2 and IL7R cause constitutive JAK/STAT activation downstream of CRLF2.
IKZF1 deletion IKAROS transcription factor signaling This results in activation of EBF1, MSH2, and MCL1, leading to B-cell leukemogenesis.[49]

Genetic Diagnostic Testing Methods

  • Flow cytometry for CRLF2 has been shown in some studies to be 100% concordant with FISH results[41].
  • Next-generation sequencing is helpful for detecting copy number changes, single nucleotide variants, and gene fusions involving CRLF2, ABL1, ABL2, JAK2, etc.
  • Gene expression profile algorithms, incorporating prediction analysis or hierarchical clustering of microarrays, provide a definitive diagnosis of B-lymphoblastic leukaemia/lymphoma with BCR::ABL1-like features.

Familial Forms

Families with certain inherited variants of GATA3 (often seen in Native-American populations) are at increased risk of B-lymphoblastic leukaemia/lymphoma with BCR::ABL1-like features.[50]

Additional Information

Clinical trial of TKI in B-lymphoblastic leukaemia/lymphoma with BCR::ABL1-like features (Clinicaltrials.gov Identifier: NCT02883049)

Clinical trial of JAK inhibitor in B-lymphoblastic leukaemia/lymphoma with BCR::ABL1-like features (Clinicaltrials.gov Identifier: NCT02723994)

Links

CRLF2

ABL1

ABL2

JAK2

PDGFRB

IKZF1

B-lymphoblastic leukaemia/lymphoma with BCR::ABL1-like features in Pathology Outlines

References

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  1. ↑ Mullighan, Charles G.; et al. (2009). "Deletion of IKZF1 and prognosis in acute lymphoblastic leukemia". The New England Journal of Medicine. 360 (5): 470–480. doi:10.1056/NEJMoa0808253. ISSN 1533-4406. PMC 2674612. PMID 19129520.
  2. ↑ Den Boer, Monique L.; et al. (2009). "A subtype of childhood acute lymphoblastic leukaemia with poor treatment outcome: a genome-wide classification study". The Lancet. Oncology. 10 (2): 125–134. doi:10.1016/S1470-2045(08)70339-5. ISSN 1474-5488. PMC 2707020. PMID 19138562.
  3. ↑ WHO Classification of Tumours Editorial Board. Hematolymphoid tumors. Lyon (France): International Agency for Research on Cancer; 2022. [cited 2025 NOV 05]. (WHO classification of tumors series, 5th ed.). Available from: https:​//tumourclassification​.iarc.who.int.
  4. ↑ Campo, Elias; et al. (2022-09-15). "The International Consensus Classification of Mature Lymphoid Neoplasms: a report from the Clinical Advisory Committee". Blood. 140 (11): 1229–1253. doi:10.1182/blood.2022015851. ISSN 1528-0020. PMC 9479027 Check |pmc= value (help). PMID 35653592 Check |pmid= value (help).
  5. ↑ 5.00 5.01 5.02 5.03 5.04 5.05 5.06 5.07 5.08 5.09 5.10 5.11 Roberts, Kathryn G.; et al. (2014-09-11). "Targetable kinase-activating lesions in Ph-like acute lymphoblastic leukemia". The New England Journal of Medicine. 371 (11): 1005–1015. doi:10.1056/NEJMoa1403088. ISSN 1533-4406. PMC 4191900. PMID 25207766.
  6. ↑ Akkari, Yassmine M. N.; et al. (2020-05). "Evidence-based review of genomic aberrations in B-lymphoblastic leukemia/lymphoma: Report from the cancer genomics consortium working group for lymphoblastic leukemia". Cancer Genetics. 243: 52–72. doi:10.1016/j.cancergen.2020.03.001. ISSN 2210-7762. PMID 32302940 Check |pmid= value (help). Check date values in: |date= (help)
  7. ↑ 7.0 7.1 7.2 7.3 7.4 7.5 7.6 7.7 7.8 Reshmi, Shalini C.; et al. (2017-06-22). "Targetable kinase gene fusions in high-risk B-ALL: a study from the Children's Oncology Group". Blood. 129 (25): 3352–3361. doi:10.1182/blood-2016-12-758979. ISSN 1528-0020. PMC 5482101. PMID 28408464.
  8. ↑ Zaliova, Marketa; et al. (2016-09). "Characterization of leukemias with ETV6-ABL1 fusion". Haematologica. 101 (9): 1082–1093. doi:10.3324/haematol.2016.144345. ISSN 1592-8721. PMC 5060025. PMID 27229714. Check date values in: |date= (help)
  9. ↑ Ernst, Thomas; et al. (2011-04). "Identification of FOXP1 and SNX2 as novel ABL1 fusion partners in acute lymphoblastic leukaemia". British Journal of Haematology. 153 (1): 43–46. doi:10.1111/j.1365-2141.2010.08457.x. ISSN 1365-2141. PMID 21391972. Check date values in: |date= (help)
  10. ↑ Duployez, Nicolas; et al. (2016-04). "NUP214-ABL1 fusion defines a rare subtype of B-cell precursor acute lymphoblastic leukemia that could benefit from tyrosine kinase inhibitors". Haematologica. 101 (4): e133–134. doi:10.3324/haematol.2015.136499. ISSN 1592-8721. PMC 5004396. PMID 26681761. Check date values in: |date= (help)
  11. ↑ Collette, Y.; et al. (2015-03-13). "Drug response profiling can predict response to ponatinib in a patient with t(1;9)(q24;q34)-associated B-cell acute lymphoblastic leukemia". Blood Cancer Journal. 5 (3): e292. doi:10.1038/bcj.2015.13. ISSN 2044-5385. PMC 4382656. PMID 25768406.
  12. ↑ Sheng, Guangying; et al. (2017). "t(1;9)(p34;q34)/SFPQ-ABL1 Fusion in a Patient with Ph-Like Common B-Cell Acute Lymphoblastic Leukemia". Acta Haematologica. 137 (1): 40–43. doi:10.1159/000452265. ISSN 1421-9662. PMID 27894117.
  13. ↑ 13.00 13.01 13.02 13.03 13.04 13.05 13.06 13.07 13.08 13.09 13.10 13.11 13.12 13.13 Tasian, Sarah K.; et al. (2017-11-09). "Philadelphia chromosome-like acute lymphoblastic leukemia". Blood. 130 (19): 2064–2072. doi:10.1182/blood-2017-06-743252. ISSN 1528-0020. PMC 5680607. PMID 28972016.
  14. ↑ Tomita, Osamu; et al. (2014-03). "Sensitivity of SNX2-ABL1 toward tyrosine kinase inhibitors distinct from that of BCR-ABL1". Leukemia Research. 38 (3): 361–370. doi:10.1016/j.leukres.2013.11.017. ISSN 1873-5835. PMID 24367893. Check date values in: |date= (help)
  15. ↑ Soler, G.; et al. (2008-06). "Fusion of ZMIZ1 to ABL1 in a B-cell acute lymphoblastic leukaemia with a t(9;10)(q34;q22.3) translocation". Leukemia. 22 (6): 1278–1280. doi:10.1038/sj.leu.2405033. ISSN 1476-5551. PMID 18007576. Check date values in: |date= (help)
  16. ↑ Raca, Gordana; et al. (2015-04). "RCSD1-ABL2 fusion resulting from a complex chromosomal rearrangement in high-risk B-cell acute lymphoblastic leukemia". Leukemia & Lymphoma. 56 (4): 1145–1147. doi:10.3109/10428194.2014.951851. ISSN 1029-2403. PMID 25098428. Check date values in: |date= (help)
  17. ↑ Tran, Thai Hoa; et al. (2018-03-13). "Prognostic impact of kinase-activating fusions and IKZF1 deletions in pediatric high-risk B-lineage acute lymphoblastic leukemia". Blood Advances. 2 (5): 529–533. doi:10.1182/bloodadvances.2017014704. ISSN 2473-9537. PMC 5851421. PMID 29507076.
  18. ↑ 18.0 18.1 Jain, Nitin; et al. (2017-02-02). "Ph-like acute lymphoblastic leukemia: a high-risk subtype in adults". Blood. 129 (5): 572–581. doi:10.1182/blood-2016-07-726588. ISSN 1528-0020. PMC 5290985. PMID 27919910.
  19. ↑ Gu, Zhaohui; et al. (2016-11-08). "Genomic analyses identify recurrent MEF2D fusions in acute lymphoblastic leukaemia". Nature Communications. 7: 13331. doi:10.1038/ncomms13331. ISSN 2041-1723. PMC 5105166. PMID 27824051.
  20. ↑ 20.0 20.1 20.2 Iacobucci, Ilaria; et al. (2016-02-08). "Truncating Erythropoietin Receptor Rearrangements in Acute Lymphoblastic Leukemia". Cancer Cell. 29 (2): 186–200. doi:10.1016/j.ccell.2015.12.013. ISSN 1878-3686. PMC 4750652. PMID 26859458.
  21. ↑ Zhang, Qi; et al. (2018-01-30). "Inhibition of mTORC1/C2 signaling improves anti-leukemia efficacy of JAK/STAT blockade in CRLF2 rearranged and/or JAK driven Philadelphia chromosome-like acute B-cell lymphoblastic leukemia". Oncotarget. 9 (8): 8027–8041. doi:10.18632/oncotarget.24261. ISSN 1949-2553. PMC 5814279. PMID 29487712.
  22. ↑ Griesinger, Frank; et al. (2005-11). "A BCR-JAK2 fusion gene as the result of a t(9;22)(p24;q11.2) translocation in a patient with a clinically typical chronic myeloid leukemia". Genes, Chromosomes & Cancer. 44 (3): 329–333. doi:10.1002/gcc.20235. ISSN 1045-2257. PMID 16001431. Check date values in: |date= (help)
  23. ↑ 23.0 23.1 Roberts, Kathryn G.; et al. (2017-09-12). "Oncogenic role and therapeutic targeting of ABL-class and JAK-STAT activating kinase alterations in Ph-like ALL". Blood Advances. 1 (20): 1657–1671. doi:10.1182/bloodadvances.2017011296. ISSN 2473-9529. PMC 5728345. PMID 29296813.
  24. ↑ Zhou, Min-hang; et al. (2012-08). "Detection of ETV6 gene rearrangements in adult acute lymphoblastic leukemia". Annals of Hematology. 91 (8): 1235–1243. doi:10.1007/s00277-012-1431-4. ISSN 1432-0584. PMID 22373549. Check date values in: |date= (help)
  25. ↑ Schwaller, Jurg (2012-12). "Modeling ETV6-JAK2-induced leukemia: insights from the zebrafish". Haematologica. 97 (12): 1783–1785. doi:10.3324/haematol.2012.080754. ISSN 1592-8721. PMC 3590083. PMID 23204479. Check date values in: |date= (help)
  26. ↑ Ding, Yang Y.; et al. (2018-09). "Clinical efficacy of ruxolitinib and chemotherapy in a child with Philadelphia chromosome-like acute lymphoblastic leukemia with GOLGA5-JAK2 fusion and induction failure". Haematologica. 103 (9): e427–e431. doi:10.3324/haematol.2018.192088. ISSN 1592-8721. PMC 6119161. PMID 29773603. Check date values in: |date= (help)
  27. ↑ 27.0 27.1 27.2 27.3 Roberts, Kathryn G.; et al. (2017-02). "High Frequency and Poor Outcome of Philadelphia Chromosome-Like Acute Lymphoblastic Leukemia in Adults". Journal of Clinical Oncology: Official Journal of the American Society of Clinical Oncology. 35 (4): 394–401. doi:10.1200/JCO.2016.69.0073. ISSN 1527-7755. PMC 5455698. PMID 27870571. Check date values in: |date= (help)
  28. ↑ Yano, Mio; et al. (2015-12). "Identification of novel kinase fusion transcripts in paediatric B cell precursor acute lymphoblastic leukaemia with IKZF1 deletion". British Journal of Haematology. 171 (5): 813–817. doi:10.1111/bjh.13757. ISSN 1365-2141. PMID 26404892. Check date values in: |date= (help)
  29. ↑ Schinnerl, Dagmar; et al. (2015-02-19). "The role of the Janus-faced transcription factor PAX5-JAK2 in acute lymphoblastic leukemia". Blood. 125 (8): 1282–1291. doi:10.1182/blood-2014-04-570960. ISSN 1528-0020. PMC 4375719. PMID 25515960.
  30. ↑ Kawamura, Machiko; et al. (2015-07). "Identification of SPAG9 as a novel JAK2 fusion partner gene in pediatric acute lymphoblastic leukemia with t(9;17)(p24;q21)". Genes, Chromosomes & Cancer. 54 (7): 401–408. doi:10.1002/gcc.22251. ISSN 1098-2264. PMID 25951811. Check date values in: |date= (help)
  31. ↑ Poitras, Jennifer L.; et al. (2008-10). "Novel SSBP2-JAK2 fusion gene resulting from a t(5;9)(q14.1;p24.1) in pre-B acute lymphocytic leukemia". Genes, Chromosomes & Cancer. 47 (10): 884–889. doi:10.1002/gcc.20585. ISSN 1098-2264. PMID 18618714. Check date values in: |date= (help)
  32. ↑ Roberts, Kathryn G.; et al. (2012-08-14). "Genetic alterations activating kinase and cytokine receptor signaling in high-risk acute lymphoblastic leukemia". Cancer Cell. 22 (2): 153–166. doi:10.1016/j.ccr.2012.06.005. ISSN 1878-3686. PMC 3422513. PMID 22897847.
  33. ↑ Steeghs, Elisabeth M. P.; et al. (2017-10-27). "JAK2 aberrations in childhood B-cell precursor acute lymphoblastic leukemia". Oncotarget. 8 (52): 89923–89938. doi:10.18632/oncotarget.21027. ISSN 1949-2553. PMC 5685720. PMID 29163799.
  34. ↑ Kobayashi, Kenichiro; et al. (2014-06). "ATF7IP as a novel PDGFRB fusion partner in acute lymphoblastic leukaemia in children". British Journal of Haematology. 165 (6): 836–841. doi:10.1111/bjh.12834. ISSN 1365-2141. PMID 24628626. Check date values in: |date= (help)
  35. ↑ Ishibashi, Takeshi; et al. (2016-03). "Ph-like ALL-related novel fusion kinase ATF7IP-PDGFRB exhibits high sensitivity to tyrosine kinase inhibitors in murine cells". Experimental Hematology. 44 (3): 177–188.e5. doi:10.1016/j.exphem.2015.11.009. ISSN 1873-2399. PMID 26703895. Check date values in: |date= (help)
  36. ↑ Zhang, Ge; et al. (2017-11-14). "Acute Lymphoblastic Leukemia Patient with Variant ATF7IP/PDGFRB Fusion and Favorable Response to Tyrosine Kinase Inhibitor Treatment: A Case Report". The American Journal of Case Reports. 18: 1204–1208. doi:10.12659/ajcr.906300. ISSN 1941-5923. PMC 5700447. PMID 29133777.
  37. ↑ Schwab, Claire; et al. (2016-05-05). "EBF1-PDGFRB fusion in pediatric B-cell precursor acute lymphoblastic leukemia (BCP-ALL): genetic profile and clinical implications". Blood. 127 (18): 2214–2218. doi:10.1182/blood-2015-09-670166. ISSN 1528-0020. PMID 26872634.
  38. ↑ 38.0 38.1 38.2 38.3 38.4 38.5 Boer, Judith M.; et al. (2015-09). "BCR-ABL1-like cases in pediatric acute lymphoblastic leukemia: a comparison between DCOG/Erasmus MC and COG/St. Jude signatures". Haematologica. 100 (9): e354–357. doi:10.3324/haematol.2015.124941. ISSN 1592-8721. PMC 4800707. PMID 26045294. Check date values in: |date= (help)
  39. ↑ Boer, Judith M.; et al. (2015). "BCR-ABL1-like cases in pediatric acute lymphoblastic leukemia: a comparison between DCOG/Erasmus MC and COG/St. Jude signatures". Haematologica. 100 (9): e354–357. doi:10.3324/haematol.2015.124941. ISSN 1592-8721. PMC 4800707. PMID 26045294.
  40. ↑ van der Veer, Arian; et al. (2013-10-10). "Independent prognostic value of BCR-ABL1-like signature and IKZF1 deletion, but not high CRLF2 expression, in children with B-cell precursor ALL". Blood. 122 (15): 2622–2629. doi:10.1182/blood-2012-10-462358. ISSN 1528-0020. PMC 3795461. PMID 23974192.
  41. ↑ 41.0 41.1 Konoplev, Sergej; et al. (2017). "CRLF2-Positive B-Cell Acute Lymphoblastic Leukemia in Adult Patients: A Single-Institution Experience". American Journal of Clinical Pathology. 147 (4): 357–363. doi:10.1093/ajcp/aqx005. ISSN 1943-7722. PMID 28340183.
  42. ↑ Koleilat, Alaa; et al. (2022-12). "Characterization of unusual iAMP21 B-lymphoblastic leukemia (iAMP21-ALL) from the Mayo Clinic and Children's Oncology Group". Genes, Chromosomes & Cancer. 61 (12): 710–719. doi:10.1002/gcc.23084. ISSN 1098-2264. PMC 9549522 Check |pmc= value (help). PMID 35771717 Check |pmid= value (help). Check date values in: |date= (help)
  43. ↑ Yoda, Akinori; et al. (2010-01-05). "Functional screening identifies CRLF2 in precursor B-cell acute lymphoblastic leukemia". Proceedings of the National Academy of Sciences of the United States of America. 107 (1): 252–257. doi:10.1073/pnas.0911726107. ISSN 1091-6490. PMC 2806782. PMID 20018760.
  44. ↑ Goulart, Hannah; et al. (2025-11). "A Phase I/II Trial of Ruxolitinib with Chemotherapy for Patients with Relapsed and/or Refractory Philadelphia-like Acute Lymphoblastic Leukemia". Clinical Lymphoma, Myeloma & Leukemia. 25 (11): 800–807. doi:10.1016/j.clml.2025.05.013. ISSN 2152-2669. PMID 40500616 Check |pmid= value (help). Check date values in: |date= (help)
  45. ↑ 45.0 45.1 Quesada A, Reynolds M, Jorgensen JL, et al. Cytokine receptor-like factor 2 (CRLF2) expression in precursor B-lymphoblastic leukemia. International Clinical Cytometry Society e-Newsletter. 2014;5(1).
  46. ↑ Jain, Sarika; et al. (2020-02). "BCR-ABL1-like B-Acute Lymphoblastic Leukemia/Lymphoma: A Comprehensive Review". Archives of Pathology & Laboratory Medicine. 144 (2): 150–155. doi:10.5858/arpa.2019-0194-RA. ISSN 1543-2165. PMID 31644323. Check date values in: |date= (help)
  47. ↑ Lee, Jae Wook; et al. (2020-07). "High incidence of RAS pathway mutations among sentinel genetic lesions of Korean pediatric BCR-ABL1-like acute lymphoblastic leukemia". Cancer Medicine. 9 (13): 4632–4639. doi:10.1002/cam4.3099. ISSN 2045-7634. PMC 7333828 Check |pmc= value (help). PMID 32378810 Check |pmid= value (help). Check date values in: |date= (help)
  48. ↑ Senapati, Jayastu; et al. (2023-05). "Philadelphia-Like Genetic Rearrangements in Adults With B-Cell ALL: Refractoriness to Chemotherapy and Response to Tyrosine Kinase Inhibitor in ABL Class Rearrangements". JCO precision oncology. 7: e2200707. doi:10.1200/PO.22.00707. ISSN 2473-4284. PMC 10309573 Check |pmc= value (help). PMID 37196217 Check |pmid= value (help). Check date values in: |date= (help)
  49. ↑ van der Veer, Arian; et al. (2013). "Independent prognostic value of BCR-ABL1-like signature and IKZF1 deletion, but not high CRLF2 expression, in children with B-cell precursor ALL". Blood. 122 (15): 2622–2629. doi:10.1182/blood-2012-10-462358. ISSN 1528-0020. PMC 3795461. PMID 23974192.
  50. ↑ Perez-Andreu, Virginia; et al. (2013). "Inherited GATA3 variants are associated with Ph-like childhood acute lymphoblastic leukemia and risk of relapse". Nature Genetics. 45 (12): 1494–1498. doi:10.1038/ng.2803. ISSN 1546-1718. PMC 4039076. PMID 24141364.

Notes

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*Citation of this Page: “B-lymphoblastic leukaemia/lymphoma with BCR::ABL1-like features”. Compendium of Cancer Genome Aberrations (CCGA), Cancer Genomics Consortium (CGC), updated 11/6/2025, https://ccga.io/index.php/HAEM5:B-lymphoblastic_leukaemia/lymphoma_with_BCR::ABL1-like_features.

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