Compendium of Cancer Genome Aberrations

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.)]]


Line 10: Line 11:


==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
Kilannin Krysiak, PhD, WashU Medicine
 
Sumire K. Kitahara, MD, Cedars-Sinai Medical Center
==WHO Classification of Disease==
==WHO Classification of Disease==


Line 32: Line 35:
|-
|-
|Subtype(s)
|Subtype(s)
|B-lymphoblastic leukaemia/lymphoma with BCR::ABL1-like features
|B-lymphoblastic leukaemia/lymphoma with ''BCR::ABL1''-like features
|}
|}


Line 40: Line 43:
|+
|+
|Acceptable
|Acceptable
|Philadelphia-like (Ph-like) B-ALL; BCR::ABL1-like B-ALL/LBL
|Philadelphia-like (Ph-like) B-ALL; ''BCR::ABL1''-like B-ALL/LBL
|-
|-
|Not Recommended
|Not Recommended
Line 48: Line 51:
==Gene Rearrangements==
==Gene Rearrangements==


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> has since recognized recurring genomic alterations associated with the diagnosis of 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 is in the process of being established. 


Put your text here and fill in the table <span style="color:#0070C0">(''Instructions: Details on clinical significance such as prognosis and other important information can be provided in the notes section. Please include references throughout the table. Do not delete the table.'')</span>
 
{| class="wikitable sortable"
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.
{| class="wikitable"
|'''3’ Partner'''
|'''5’ Partner'''
|'''Chromosome rearrangement'''
|'''Gene fusion'''
|'''Visible by G-banding'''
|'''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>
|
|-
|-
!Driver Gene!!Fusion(s) and Common Partner Genes!!Molecular Pathogenesis!!Typical Chromosomal Alteration(s)
|''STRN3''
!Prevalence -Common >20%, Recurrent 5-20% or Rare <5% (Disease)
|t(9;14)(p24.1;q12)
!Diagnostic, Prognostic, and Therapeutic Significance - D, P, T
|''STRN3::JAK2'' on der(9)
!Established Clinical Significance Per Guidelines - Yes or No (Source)
|YES
!Clinical Relevance Details/Other Notes
|<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>
|
|-
|-
|<span class="blue-text">EXAMPLE:</span> ''ABL1''||<span class="blue-text">EXAMPLE:</span> ''BCR::ABL1''||<span class="blue-text">EXAMPLE:</span> The pathogenic derivative is the der(22) resulting in fusion of 5’ BCR and 3’ABL1.||<span class="blue-text">EXAMPLE:</span> t(9;22)(q34;q11.2)
|''TERF2''
|<span class="blue-text">EXAMPLE:</span> Common (CML)
|t(9;16)(p24.1;q22.1)
|<span class="blue-text">EXAMPLE:</span> D, P, T
|''TERF2::JAK2'' on der(9)
|<span class="blue-text">EXAMPLE:</span> Yes (WHO, NCCN)
|YES
|<span class="blue-text">EXAMPLE:</span>
|<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>
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). BCR::ABL1 is generally favorable in CML (add reference).
|
|-
|-
|<span class="blue-text">EXAMPLE:</span> ''CIC''
|''TPR''
|<span class="blue-text">EXAMPLE:</span> ''CIC::DUX4''
|t(1;9)(q31.1;p24.1)
|<span class="blue-text">EXAMPLE:</span> Typically, the last exon of ''CIC'' is fused to ''DUX4''. The fusion breakpoint in ''CIC'' is usually intra-exonic and removes an inhibitory sequence, upregulating ''PEA3'' genes downstream of ''CIC'' including ''ETV1'', ''ETV4'', and ''ETV5''.
|''TPR::JAK2'' on der(9)
|<span class="blue-text">EXAMPLE:</span> t(4;19)(q25;q13)
|YES
|<span class="blue-text">EXAMPLE:</span> Common (CIC-rearranged sarcoma)
|<ref name=":9" />
|<span class="blue-text">EXAMPLE:</span> D
|
|
|<span class="blue-text">EXAMPLE:</span>
''DUX4'' has many homologous genes; an alternate translocation in a minority of cases is t(10;19), but this is usually indistinguishable from t(4;19) by short-read sequencing (add references).
|-
|-
|<span class="blue-text">EXAMPLE:</span> ''ALK''
|''USP25''
|<span class="blue-text">EXAMPLE:</span> ''ELM4::ALK''
|t(9;21)(p24.1;q21.1)
 
|''USP25::JAK2''
 
|? YES
Other fusion partners include ''KIF5B, NPM1, STRN, TFG, TPM3, CLTC, KLC1''
|<ref name=":2" />
|<span class="blue-text">EXAMPLE:</span> Fusions result in constitutive activation of the ''ALK'' tyrosine kinase. The most common ''ALK'' fusion is ''EML4::ALK'', with breakpoints in intron 19 of ''ALK''. At the transcript level, a variable (5’) partner gene is fused to 3’ ''ALK'' at exon 20. Rarely, ''ALK'' fusions contain exon 19 due to breakpoints in intron 18.
|Requires complex rearrangement due to incompatible orientation of genes with respect to chromosome arms
|<span class="blue-text">EXAMPLE:</span> N/A
|-
|<span class="blue-text">EXAMPLE:</span> Rare (Lung adenocarcinoma)
|''ZBTB46''
|<span class="blue-text">EXAMPLE:</span> T
|t(9;20)(p24.1;q13.3)
|''ZBTB46::JAK2'' on der(9)
|NO
|<ref name=":10" />
|
|
|<span class="blue-text">EXAMPLE:</span>
Both balanced and unbalanced forms are observed by FISH (add references).
|-
|-
|<span class="blue-text">EXAMPLE:</span> ''ABL1''
|''ZNF274''
|<span class="blue-text">EXAMPLE:</span> N/A
|t(9;19)(p24.1;q13.4)
|<span class="blue-text">EXAMPLE:</span> Intragenic deletion of exons 2–7 in ''EGFR'' removes the ligand-binding domain, resulting in a constitutively active tyrosine kinase with downstream activation of multiple oncogenic pathways.
|''ZNF274::JAK2''
|<span class="blue-text">EXAMPLE:</span> N/A
|NO
|<span class="blue-text">EXAMPLE:</span> Recurrent (IDH-wildtype Glioblastoma)
|<ref name=":2" />
|<span class="blue-text">EXAMPLE:</span> D, P, T
|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" />
|
|
|-
|''[[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
|-
|''TMEM2''
|t(8;9)(p21.2;q21.1)
|''TMEM2::PTK2B'' on der(8)
|YES
|<ref name=":10" />
|
|
|-
| rowspan="3" |'''''TYK2''''' (19p13.2)
|''MYB''
|t(6;19)(q23.3;p13.2)
|''MYB::TYK2'' on der(6)
|YES
|<ref name=":13" />
|
|
|-
|''SMARCA4''
|inv(19)(p13.2p13.2)
|''SMARCA4::TYK2''
|NO
|<ref name=":10" />
|
|
|-
|''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
|}
|}


<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">{{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>.
**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">{{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>.
*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">{{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>.
**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">{{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>.
*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">{{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>.
**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==
==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 rearrangements. Details on clinical significance such as prognosis and other important information can be provided in the notes section. Can refer to CGC workgroup tables as linked on the homepage if applicable. Please include references throughout the table. Do not delete the table.'') </span>
{| class="wikitable sortable"
{| class="wikitable sortable"
|-
|-
Line 148: Line 534:
!Clinical Relevance Details/Other Notes
!Clinical Relevance Details/Other Notes
|-
|-
|<span class="blue-text">EXAMPLE:</span>
|5
7
|Loss
|<span class="blue-text">EXAMPLE:</span> Loss
|chr5:158,695,920-159,099,916
|<span class="blue-text">EXAMPLE:</span>
[GRCh38/hg38]
chr7
|''EBF1''
|<span class="blue-text">EXAMPLE:</span>
|Unknown
Unknown
|No
|<span class="blue-text">EXAMPLE:</span> D, P
|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> No
|-
|<span class="blue-text">EXAMPLE:</span>
|7
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 references).
|Loss
|chr7:50,303,455-50,405,101
[GRCh38/hg38]
|''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>
|-
|9
|Loss
|chr9:21,967,752-21,995,324/
chr9:22,002,903-22,009,313
 
[GRCh38/hg38]
|''CDKN2A/B''
|Unknown
|No
|Deletion of ''CDKN2A/B'' results in altered B-cell development.<ref name=":4" />
|-
|9
|Loss
|chr9:36,833,269-37,034,268
[GRCh38/hg38]
|''PAX5''
|Unknown
|No
|Deletion of ''PAX5'' results in altered B-cell development.<ref name=":4" />
|-
|-
|<span class="blue-text">EXAMPLE:</span>
|12
8
|Loss
|<span class="blue-text">EXAMPLE:</span> Gain
|chr12:11,649,674-11,895,377
|<span class="blue-text">EXAMPLE:</span>
[GRCh38/hg38]
chr8
|''ETV6''
|<span class="blue-text">EXAMPLE:</span>
|Unknown
Unknown
|No
|<span class="blue-text">EXAMPLE:</span> D, P
|Deletion of ''ETV6'' results in altered B-cell development.<ref name=":4" />
|
|<span class="blue-text">EXAMPLE:</span>
Common recurrent secondary finding for t(8;21) (add references).
|-
|-
|<span class="blue-text">EXAMPLE:</span>
|13
17
|Loss
|<span class="blue-text">EXAMPLE:</span> Amp
|chr13:48,303,744-48,599,436
|<span class="blue-text">EXAMPLE:</span>
[GRCh38/hg38]
17q12; chr17:39,700,064-39,728,658 [hg38; 28.6 kb]
|''RB1''
|<span class="blue-text">EXAMPLE:</span>
|Unknown
''ERBB2''
|No
|<span class="blue-text">EXAMPLE:</span> D, P, T
|Deletion of ''RB1'' results in disrupted cell-cycle regulation.<ref name=":4" />
|
|<span class="blue-text">EXAMPLE:</span>
Amplification of ''ERBB2'' is associated with HER2 overexpression in HER2 positive breast cancer (add references). Add criteria for how amplification is defined.
|-
|-
|
|17
|
|Loss
|
|chr17:7,661,779-7,687,546
|
[GRCh38/hg38]
|
|''TP53''
|
|Unknown
|
|No
|Deletion of ''TP53'' results in in disrupted cell-cycle regulation.<ref name=":4" />
|}
|}


<blockquote class="blockedit">{{Box-round|title=v4:Genomic Gain/Loss/LOH|The content below was from the old template. Please incorporate above.}}</blockquote>
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">{{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>.
<blockquote class="blockedit">
<center><span style="color:Maroon">'''End of V4 Section'''</span>
----
</blockquote>
==Characteristic Chromosomal or Other Global Mutational Patterns==
==Characteristic Chromosomal or Other Global Mutational Patterns==


Put your text here and fill in the table <span style="color:#0070C0">(I''nstructions: Included in this category are alterations such as 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; microsatellite instability; homologous recombination deficiency; mutational signature pattern; etc. Details on clinical significance such as prognosis and other important information can be provided in the notes section. Please include references throughout the table. Do not delete the table.'')</span>
{| class="wikitable sortable"
{| class="wikitable sortable"
|-
|-
Line 216: Line 615:
Co-deletion of 1p and 18q
Co-deletion of 1p and 18q
|<span class="blue-text">EXAMPLE:</span> See chromosomal rearrangements table as this pattern is due to an unbalanced derivative translocation associated with oligodendroglioma (add reference).
|<span class="blue-text">EXAMPLE:</span> See chromosomal rearrangements table as this pattern is due to an unbalanced derivative translocation associated with oligodendroglioma (add reference).
|<span class="blue-text">EXAMPLE:</span> Common (Oligodendroglioma)
|Common (Oligodendroglioma)
|<span class="blue-text">EXAMPLE:</span> D, P
|Unknown
|
|
|
|
Line 224: Line 623:
Microsatellite instability - hypermutated  
Microsatellite instability - hypermutated  
|
|
|<span class="blue-text">EXAMPLE:</span> Common (Endometrial carcinoma)
|Rare (<5%)
|<span class="blue-text">EXAMPLE:</span> P, T
|<span class="blue-text">EXAMPLE:</span> P, T
|
|
Line 241: Line 640:
[[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]]


[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]
[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]
Line 309: Line 708:
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>.
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" />.
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">{{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>.


<blockquote class="blockedit">
<blockquote class="blockedit">
Line 320: Line 719:
==Genes and Main Pathways Involved==
==Genes and Main Pathways Involved==


Put your text here and fill in the table <span style="color:#0070C0">(''Instructions: Please include references throughout the table. Do not delete the 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 response 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'', ''IL7R, SH2B3, IL2RB, and TYK2''; ''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
|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" />; other mutations not in ''CRLF2'' and ''IL7R'' result in 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 the 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==
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[[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==
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<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.
<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.


Prior Author(s):   
Prior Author(s):  Fabiola Quintero-Rivera, MD 
 


          
          
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