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 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" /><ref name=":0" /> 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 recognized recurring, genomic alterations associated with the diagnosis of B-lymphoblastic leukaemia/lymphoma with ''BCR::ABL1''-like features, including  ABL1-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''
<blockquote class="blockedit">{{Box-round|title=v4:Chromosomal Rearrangements (Gene Fusions)|The content below was from the old template. Please incorporate above.}}</blockquote>
|t(19;20)(p13.2;q13.3)
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>.
|''ZNF340::TYK2''
 
|NO
<blockquote class="blockedit">
|<ref name=":10" />
<center><span style="color:Maroon">'''End of V4 Section'''</span>
|Requires complex rearrangement due to incompatible orientation of genes with respect to chromosome arms
----
|}<blockquote class="blockedit"><center>
</blockquote>
</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:
<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)
* Chromosomal Rearrangements (Gene Fusions)
Line 159: Line 566:
|<span class="blue-text">EXAMPLE:</span>
|<span class="blue-text">EXAMPLE:</span>
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).
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).
|-
|<span class="blue-text">EXAMPLE:</span>
8
|<span class="blue-text">EXAMPLE:</span> Gain
|<span class="blue-text">EXAMPLE:</span>
chr8
|<span class="blue-text">EXAMPLE:</span>
Unknown
|<span class="blue-text">EXAMPLE:</span> D, P
|
|<span class="blue-text">EXAMPLE:</span>
Common recurrent secondary finding for t(8;21) (add references).
|-
|<span class="blue-text">EXAMPLE:</span>
17
|<span class="blue-text">EXAMPLE:</span> Amp
|<span class="blue-text">EXAMPLE:</span>
17q12; chr17:39,700,064-39,728,658 [hg38; 28.6 kb]
|<span class="blue-text">EXAMPLE:</span>
''ERBB2''
|<span class="blue-text">EXAMPLE:</span> D, P, T
|
|<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.
|-
|
|
|
|
|
|
|
|}
|}


Line 241: Line 616:
[[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 389: Line 764:
<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 
 


          
          

Revision as of 10:16, 5 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

Kilannin Krysiak, PhD, WashU Medicine

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] has recognized recurring, genomic alterations associated with the diagnosis of B-lymphoblastic leukaemia/lymphoma with BCR::ABL1-like features, including ABL1-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 is in the process of 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
editv4: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)
  • 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[2].
    • 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[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[38].
    • 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[39].
  • 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[40].
    • 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[38][41][42].
End of V4 Section

Individual Region Genomic Gain/Loss/LOH

Put your text here and fill in the table (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.)

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
EXAMPLE:

7

EXAMPLE: Loss EXAMPLE:

chr7

EXAMPLE:

Unknown

EXAMPLE: D, P EXAMPLE: No EXAMPLE:

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).

editv4:Genomic Gain/Loss/LOH
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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[43].

End of V4 Section

Characteristic Chromosomal or Other Global Mutational Patterns

Put your text here and fill in the table (Instructions: 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.)

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
EXAMPLE:

Co-deletion of 1p and 18q

EXAMPLE: See chromosomal rearrangements table as this pattern is due to an unbalanced derivative translocation associated with oligodendroglioma (add reference). EXAMPLE: Common (Oligodendroglioma) EXAMPLE: D, P
EXAMPLE:

Microsatellite instability - hypermutated

EXAMPLE: Common (Endometrial carcinoma) EXAMPLE: P, T
editv4:Characteristic Chromosomal Aberrations / Patterns
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Approximately half of cases demonstrate rearrangements resulting in overexpression of CRLF2[44]. 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.

[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]

[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)

End of V4 Section

Gene Mutations (SNV/INDEL)

Put your text here and fill in the table (Instructions: This table is not meant to be an exhaustive list; please include only genes/alterations that are recurrent or common as well either disease defining and/or clinically significant. If a gene has multiple mechanisms depending on the type or site of the alteration, add multiple entries 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. Details on clinical significance such as prognosis and other important information such as concomitant and mutually exclusive mutations can be provided in the notes section. Please include references throughout the table. Do not delete the table.)

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
EXAMPLE:EGFR


EXAMPLE: Exon 18-21 activating mutations EXAMPLE: Oncogene EXAMPLE: Common (lung cancer) EXAMPLE: T EXAMPLE: Yes (NCCN) EXAMPLE: Exons 18, 19, and 21 mutations are targetable for therapy. Exon 20 T790M variants cause resistance to first generation TKI therapy and are targetable by second and third generation TKIs (add references).
EXAMPLE: TP53; Variable LOF mutations


EXAMPLE: Variable LOF mutations EXAMPLE: Tumor Supressor Gene EXAMPLE: Common (breast cancer) EXAMPLE: P EXAMPLE: >90% are somatic; rare germline alterations associated with Li-Fraumeni syndrome (add reference). Denotes a poor prognosis in breast cancer.
EXAMPLE: BRAF; Activating mutations EXAMPLE: Activating mutations EXAMPLE: Oncogene EXAMPLE: Common (melanoma) EXAMPLE: T

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.

editv4:Gene Mutations (SNV/INDEL)
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In addition to gene translocations, gain-of-function mutations in CRLF2 itself or in its partner gene, IL7RA, have been seen[45]. Alternative alterations activating kinase signaling occur, including activating mutations of FLT3, as well as focal deletions of SH2B3 (also known as LNK)[46].

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[39].

End of V4 Section

Epigenomic Alterations

Not applicable

Genes and Main Pathways Involved

Put your text here and fill in the table (Instructions: Please include references throughout the table. Do not delete the table.)

Gene; Genetic Alteration Pathway Pathophysiologic Outcome
EXAMPLE: BRAF and MAP2K1; Activating mutations EXAMPLE: MAPK signaling EXAMPLE: Increased cell growth and proliferation
EXAMPLE: CDKN2A; Inactivating mutations EXAMPLE: Cell cycle regulation EXAMPLE: Unregulated cell division
EXAMPLE: KMT2C and ARID1A; Inactivating mutations EXAMPLE: Histone modification, chromatin remodeling EXAMPLE: Abnormal gene expression program
editv4:Genes and Main Pathways Involved
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  • IKAROS transcription factor: Deletion of IKZF1 results in activation of EBF1, MSH2, and MCL1, leading to B-cell leukemogenesis[47].
  • 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[45].
  • Dysregulation of several tyrosine kinase signaling pathways (involving ABL1, ABL2, PDGFRB, CSF1, etc.) results in B-cell progenitor proliferation.
End of V4 Section

Genetic Diagnostic Testing Methods

  • Flow cytometry for CRLF2 has been shown in some studies to be 100% concordant with FISH results[44].
  • 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.

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[48].

Additional Information

Put your text here

Links

CRLF2

ABL1

ABL2

JAK2

PDGFRB

IKZF1

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

References

(use the "Cite" icon at the top of the page) (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.)

  1. ↑ 1.0 1.1 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. ↑ 2.0 2.1 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 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 Roberts, Kathryn G.; et al. (2014). "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.
  39. ↑ 39.0 39.1 Herold, Tobias; et al. (2017). "Adults with Philadelphia chromosome-like acute lymphoblastic leukemia frequently have IGH-CRLF2 and JAK2 mutations, persistence of minimal residual disease and poor prognosis". Haematologica. 102 (1): 130–138. doi:10.3324/haematol.2015.136366. ISSN 1592-8721. PMC 5210243. PMID 27561722.
  40. ↑ Jain, Nitin; et al. (2017). "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.
  41. ↑ Tasian, Sarah K.; et al. (2012). "Aberrant STAT5 and PI3K/mTOR pathway signaling occurs in human CRLF2-rearranged B-precursor acute lymphoblastic leukemia". Blood. 120 (4): 833–842. doi:10.1182/blood-2011-12-389932. ISSN 1528-0020. PMC 3412346. PMID 22685175.
  42. ↑ Iacobucci, Ilaria; et al. (2016). "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.
  43. ↑ 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.
  44. ↑ 44.0 44.1 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.
  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. ↑ Tosi S & Reid AG. The Genetic Basis of Haematological Cancers. John Wiley & Sons, Incorporated: Chichester, United Kingdom: 2016.
  47. ↑ 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.
  48. ↑ 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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Prior Author(s): Fabiola Quintero-Rivera, MD


*Citation of this Page: “B-lymphoblastic leukaemia/lymphoma with BCR::ABL1-like features”. Compendium of Cancer Genome Aberrations (CCGA), Cancer Genomics Consortium (CGC), updated 11/5/2025, https://ccga.io/index.php/HAEM5:B-lymphoblastic_leukaemia/lymphoma_with_BCR::ABL1-like_features.

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