HAEM5:B-lymphoblastic leukaemia/lymphoma with BCR::ABL1-like features - Revision history

Sumire.Kitahara at 23:15, 14 February 2026

2026-02-14T23:15:00Z

← Older revision		Revision as of 18:15, 14 February 2026
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	==Primary Author(s)*==		==Primary Author(s)*==
	Mark G. Evans, MD, Caris Life Sciences		Mark G. Evans, MD, Caris Life Sciences

			Sumire Kitahara, MD, Cedars-Sinai, Los Angeles
	==WHO Classification of Disease==		==WHO Classification of Disease==

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

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

	<nowiki>*</nowiki>''Citation of this Page'': “B-lymphoblastic leukaemia/lymphoma with BCR::ABL1-like features”. Compendium of Cancer Genome Aberrations (CCGA), Cancer Genomics Consortium (CGC), updated {{REVISIONMONTH}}/{{REVISIONDAY}}/{{REVISIONYEAR}}, <nowiki>https://ccga.io/index.php/HAEM5:B-lymphoblastic_leukaemia/lymphoma_with_BCR::ABL1-like_features</nowiki>.		<nowiki>*</nowiki>''Citation of this Page'': Evans MG, Kitahara S. “B-lymphoblastic leukaemia/lymphoma with BCR::ABL1-like features”. Compendium of Cancer Genome Aberrations (CCGA), Cancer Genomics Consortium (CGC), updated {{REVISIONMONTH}}/{{REVISIONDAY}}/{{REVISIONYEAR}}, <nowiki>https://ccga.io/index.php/HAEM5:B-lymphoblastic_leukaemia/lymphoma_with_BCR::ABL1-like_features</nowiki>.
	[[Category:HAEM5]]		[[Category:HAEM5]]
	[[Category:DISEASE]]		[[Category:DISEASE]]
	[[Category:Diseases B]]		[[Category:Diseases B]]

Sumire.Kitahara at 22:51, 14 February 2026

2026-02-14T22:51:22Z

← Older revision		Revision as of 17:51, 14 February 2026
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	[[HAEM5:Table_of_Contents\|Haematolymphoid Tumours (WHO Classification, 5th ed.)]]		[[HAEM5:Table_of_Contents\|Haematolymphoid Tumours (WHO Classification, 5th ed.)]]

	~~{{Under Construction}}~~

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

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

	==Primary Author(s)*==		==Primary Author(s)*==
	Mark G. Evans, MD, Caris Life Sciences		Mark G. Evans, MD, Caris Life Sciences

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

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	\|P		\|P
	\|No		\|No
	\|Chromosome X/Y abnormalities include either translocation of the immunoglobin heavy chain enhance locus into ''CRLF2'' (''IGH''::''CRLF2''—more commonly seen in adults) or a cryptic deletion involving the PAR1 ~~psuedoautosomal~~ region, resulting in fusion of ''CRLF2'' and ''P2RY8'' (more commonly seen in children); these alterations involving ''CRLF2'' have been associated with poor survival;<ref name=":7">{{Cite journal\|last=Konoplev\|first=Sergej\|last2=Lu\|first2=Xinyan\|last3=Konopleva\|first3=Marina\|last4=Jain\|first4=Nitin\|last5=Ouyang\|first5=Juan\|last6=Goswami\|first6=Maitrayee\|last7=Roberts\|first7=Kathryn G.\|last8=Valentine\|first8=Marc\|last9=Mullighan\|first9=Charles G.\|date=2017\|title=CRLF2-Positive B-Cell Acute Lymphoblastic Leukemia in Adult Patients: A Single-Institution Experience\|url=https://www.ncbi.nlm.nih.gov/pubmed/28340183\|journal=American Journal of Clinical Pathology\|volume=147\|issue=4\|pages=357–363\|doi=10.1093/ajcp/aqx005\|issn=1943-7722\|pmid=28340183}}</ref> very rare alternative translocations involving ''CRLF2'' have also been observed.		\|Chromosome X/Y abnormalities include either translocation of the immunoglobin heavy chain enhance locus into ''CRLF2'' (''IGH''::''CRLF2''—more commonly seen in adults) or a cryptic deletion involving the PAR1 pseudoautosomal region, resulting in fusion of ''CRLF2'' and ''P2RY8'' (more commonly seen in children); these alterations involving ''CRLF2'' have been associated with poor survival;<ref name=":7">{{Cite journal\|last=Konoplev\|first=Sergej\|last2=Lu\|first2=Xinyan\|last3=Konopleva\|first3=Marina\|last4=Jain\|first4=Nitin\|last5=Ouyang\|first5=Juan\|last6=Goswami\|first6=Maitrayee\|last7=Roberts\|first7=Kathryn G.\|last8=Valentine\|first8=Marc\|last9=Mullighan\|first9=Charles G.\|date=2017\|title=CRLF2-Positive B-Cell Acute Lymphoblastic Leukemia in Adult Patients: A Single-Institution Experience\|url=https://www.ncbi.nlm.nih.gov/pubmed/28340183\|journal=American Journal of Clinical Pathology\|volume=147\|issue=4\|pages=357–363\|doi=10.1093/ajcp/aqx005\|issn=1943-7722\|pmid=28340183}}</ref> very rare alternative translocations involving ''CRLF2'' have also been observed.
	\|-		\|-
	\|Polysomy or iAMP21		\|Polysomy or iAMP21

Mark.Evans: /* Primary Author(s)* */

2025-11-06T21:08:54Z

Primary Author(s)*

← Older revision		Revision as of 16:08, 6 November 2025
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	==Primary Author(s)*==		==Primary Author(s)*==
	Mark G. Evans, MD, Caris Life Sciences		Mark G. Evans, MD, Caris Life Sciences

	~~Kilannin Krysiak, PhD, WashU Medicine~~

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

Mark.Evans: /* Genes and Main Pathways Involved */

2025-11-06T14:29:55Z

Genes and Main Pathways Involved

← Older revision		Revision as of 09:29, 6 November 2025
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	\|These result in B-cell progenitor proliferation; may be responsive to TKIs.<ref>{{Cite journal\|last=Senapati\|first=Jayastu\|last2=Jabbour\|first2=Elias\|last3=Konopleva\|first3=Marina\|last4=Short\|first4=Nicholas J.\|last5=Tang\|first5=Guilin\|last6=Daver\|first6=Naval\|last7=Kebriaei\|first7=Partow\|last8=Kadia\|first8=Tapan\|last9=Pemmaraju\|first9=Naveen\|date=2023-05\|title=Philadelphia-Like Genetic Rearrangements in Adults With B-Cell ALL: Refractoriness to Chemotherapy and Response to Tyrosine Kinase Inhibitor in ABL Class Rearrangements\|url=https://pubmed.ncbi.nlm.nih.gov/37196217\|journal=JCO precision oncology\|volume=7\|pages=e2200707\|doi=10.1200/PO.22.00707\|issn=2473-4284\|pmc=10309573\|pmid=37196217}}</ref>		\|These result in B-cell progenitor proliferation; may be responsive to TKIs.<ref>{{Cite journal\|last=Senapati\|first=Jayastu\|last2=Jabbour\|first2=Elias\|last3=Konopleva\|first3=Marina\|last4=Short\|first4=Nicholas J.\|last5=Tang\|first5=Guilin\|last6=Daver\|first6=Naval\|last7=Kebriaei\|first7=Partow\|last8=Kadia\|first8=Tapan\|last9=Pemmaraju\|first9=Naveen\|date=2023-05\|title=Philadelphia-Like Genetic Rearrangements in Adults With B-Cell ALL: Refractoriness to Chemotherapy and Response to Tyrosine Kinase Inhibitor in ABL Class Rearrangements\|url=https://pubmed.ncbi.nlm.nih.gov/37196217\|journal=JCO precision oncology\|volume=7\|pages=e2200707\|doi=10.1200/PO.22.00707\|issn=2473-4284\|pmc=10309573\|pmid=37196217}}</ref>
	\|-		\|-
	\|''CRLF2'' overexpression; mutations of ''CRLF2'', ''JAK1'', ''IL7R, SH2B3, IL2RB, TYK2,'' and ''TLSP''; ''JAK2'' and ''EPOR'' rearrangements		\|''CRLF2'' overexpression; mutations of ''CRLF2'', ''JAK1/2'', ''IL7R, SH2B3, IL2RB, TYK2,'' and ''TLSP''; ''JAK2'' and ''EPOR'' rearrangements
	\|JAK-STAT signaling		\|JAK-STAT signaling
	\|These potentiate the JAK2-signal transducer and upregulate the transcription 5 pathway;<ref name=":8" /> other mutations not in ''CRLF2'' and ''IL7R'' cause constitutive JAK/STAT activation downstream of CRLF2.		\|These potentiate the JAK2-signal transducer and upregulate the transcription 5 pathway;<ref name=":8" /> other mutations not in ''CRLF2'' and ''IL7R'' cause constitutive JAK/STAT activation downstream of CRLF2.

Mark.Evans: /* Gene Mutations (SNV/INDEL) */

2025-11-06T14:28:42Z

Gene Mutations (SNV/INDEL)

← Older revision		Revision as of 09:28, 6 November 2025
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	\|''SH2B3''		\|''SH2B3''
	''IL2RB''		''IL2RB''

	''TYK2''		''TYK2''

	''TLSP''		''TLSP''
	\|Activating mutations		\|Activating mutations

Mark.Evans at 23:25, 5 November 2025

2025-11-05T23:25:05Z

← Older revision		Revision as of 18:25, 5 November 2025
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	\|'''Comment'''		\|'''Comment'''
	\|-		\|-
	\| rowspan="12" \|~~'''~~''[[ABL1]]~~'''~~''		\| rowspan="12" \|''[[ABL1]]''
	(9q34)		(9q34)
	\|''CENPC1''		\|''CENPC1''
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	\|		\|
	\|-		\|-
	\| rowspan="3" \|~~'''~~''[[ABL2]]~~'''~~''		\| rowspan="3" \|''[[ABL2]]''
	(1q25.2)		(1q25.2)
	\|''PAG1''		\|''PAG1''
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	\|		\|
	\|-		\|-
	\| rowspan="2" \|~~'''~~''[[CRLF2]]~~'''~~''		\| rowspan="2" \|''[[CRLF2]]''
	(Xp22.3 & Yp11.3)		(Xp22.3 & Yp11.3)
	\|''[[IGH]]''		\|''[[IGH]]''
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	\|		\|
	\|-		\|-
	\| rowspan="3" \|~~'''~~''CSF1R~~'''~~''		\| rowspan="3" \|''CSF1R''
	(5q32)		(5q32)
	\|''MEF2D''		\|''MEF2D''
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	\|		\|
	\|-		\|-
	\|~~'''~~''DGKH~~'''~~'' (13q14.1)		\|''DGKH'' (13q14.1)
	\|''ZFAND3''		\|''ZFAND3''
	\|t(6;13)(p21.2;q14.1)		\|t(6;13)(p21.2;q14.1)
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	\|Requires complex rearrangement due to incompatible orientation of genes with respect to chromosome arms		\|Requires complex rearrangement due to incompatible orientation of genes with respect to chromosome arms
	\|-		\|-
	\| rowspan="4" \|~~'''~~''EPOR~~'''~~'' (19p13.2)		\| rowspan="4" \|''EPOR'' (19p13.2)
	\|''[[IGH]]''		\|''[[IGH]]''
	\|ins(14;19)(q32;p13.2p13.2)		\|ins(14;19)(q32;p13.2p13.2)
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	\|		\|
	\|-		\|-
	\|~~'''~~''IL2RB~~'''~~'' (22q12.3)		\|''IL2RB'' (22q12.3)
	\|''MYH9''		\|''MYH9''
	\|22q12.3 rearrangement		\|22q12.3 rearrangement
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	\|On the same chromosome arm; however, a simple deletion cannot cause the fusion due to the orientation of genes		\|On the same chromosome arm; however, a simple deletion cannot cause the fusion due to the orientation of genes
	\|-		\|-
	\| rowspan="22" \|~~'''~~''[[JAK2]]~~'''~~''		\| rowspan="22" \|''[[JAK2]]''
	(9p24.1)		(9p24.1)
	\|''ATF7IP''		\|''ATF7IP''
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	\|		\|
	\|-		\|-
	\|~~'''~~''[[PDGFRA]]~~'''~~''		\|''[[PDGFRA]]''
	(4q12)		(4q12)
	\|''FIP1L1''		\|''FIP1L1''
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	\|Interstitial deletion. Seen also in myeloid/lymphoid neoplasms with eosinophilia		\|Interstitial deletion. Seen also in myeloid/lymphoid neoplasms with eosinophilia
	\|-		\|-
	\| rowspan="8" \|~~'''~~''[[PDGFRB]]~~'''~~'' (5q32)		\| rowspan="8" \|''[[PDGFRB]]'' (5q32)
	\|''ATF7IP''		\|''ATF7IP''
	\|t(5;12)(q32;p13.1)		\|t(5;12)(q32;p13.1)
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	\|		\|
	\|-		\|-
	\| rowspan="3" \|~~'''~~''PTK2B~~'''~~'' (8p21.2)		\| rowspan="3" \|''PTK2B'' (8p21.2)
	\|''[[KDM6A]]''		\|''[[KDM6A]]''
	\|t(X;8)(p11.3;p21.2)		\|t(X;8)(p11.3;p21.2)
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	\|		\|
	\|-		\|-
	\| rowspan="3" \|~~'''~~''TYK2~~'''~~'' (19p13.2)		\| rowspan="3" \|''TYK2'' (19p13.2)
	\|''MYB''		\|''MYB''
	\|t(6;19)(q23.3;p13.2)		\|t(6;19)(q23.3;p13.2)

Mark.Evans at 23:20, 5 November 2025

2025-11-05T23:20:54Z

← Older revision		Revision as of 18:20, 5 November 2025
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	\|Unknown		\|Unknown
	\|No		\|No
	\|Half of cases with ''CRLF2'' overexpression have activating mutations in ''JAK1'' or ''JAK2'' that promote downstream JAK-STAT signaling;<ref name=":10" /> the most common mutation, p.R683G, occurs in the pseudokinase domain of ''JAK2'', and less common ''JAK1'' alterations have been detected, which include p.V658F most frequently.		\|Half of cases with ''CRLF2'' overexpression have activating mutations in ''JAK1'' or ''JAK2'' that promote downstream JAK-STAT signaling;<ref name=":10" /> the most common mutation, p.R683G, occurs in the pseudokinase domain of ''JAK2'', and less common ''JAK1'' alterations have been detected, which include p.V658F most frequently; clinical trials examining the treatment effects of targeting JAK proteins are currently ongoing.<ref>{{Cite journal\|last=Goulart\|first=Hannah\|last2=Jabbour\|first2=Elias\|last3=Short\|first3=Nicholas J.\|last4=Kadia\|first4=Tapan M.\|last5=Pemmaraju\|first5=Naveen\|last6=Takahashi\|first6=Koichi\|last7=Ravandi\|first7=Farhad\|last8=Konopleva\|first8=Marina\|last9=Jain\|first9=Nitin\|date=2025-11\|title=A Phase I/II Trial of Ruxolitinib with Chemotherapy for Patients with Relapsed and/or Refractory Philadelphia-like Acute Lymphoblastic Leukemia\|url=https://pubmed.ncbi.nlm.nih.gov/40500616\|journal=Clinical Lymphoma, Myeloma & Leukemia\|volume=25\|issue=11\|pages=800–807\|doi=10.1016/j.clml.2025.05.013\|issn=2152-2669\|pmid=40500616}}</ref>
	\|-		\|-
	\|''IL7R''		\|''IL7R''

Mark.Evans at 23:11, 5 November 2025

2025-11-05T23:11:02Z

← Older revision		Revision as of 18:11, 5 November 2025
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	\|''IL7R'' is the partner gene of ''CRLF2''; gain-of-function mutations potentiate CRFL2 and its cofactor IL7RA forming a receptor for thymic stromal-derived lymphopoietin, leading to JAK-STAT activation.<ref name=":8">Quesada A, Reynolds M, Jorgensen JL, et al. Cytokine receptor-like factor 2 (CRLF2) expression in precursor B-lymphoblastic leukemia. International Clinical Cytometry Society e-Newsletter. 2014;5(1).</ref>		\|''IL7R'' is the partner gene of ''CRLF2''; gain-of-function mutations potentiate CRFL2 and its cofactor IL7RA forming a receptor for thymic stromal-derived lymphopoietin, leading to JAK-STAT activation.<ref name=":8">Quesada A, Reynolds M, Jorgensen JL, et al. Cytokine receptor-like factor 2 (CRLF2) expression in precursor B-lymphoblastic leukemia. International Clinical Cytometry Society e-Newsletter. 2014;5(1).</ref>
	\|-		\|-
	\|''SH2B3'', ''IL2RB'', ''TYK2''~~, and~~ ''TLSP''		\|''SH2B3''
			''IL2RB''
			''TYK2''
			''TLSP''
	\|Activating mutations		\|Activating mutations
	\|Oncogene		\|Oncogene

Mark.Evans at 22:43, 5 November 2025

2025-11-05T22:43:42Z

← Older revision		Revision as of 17:43, 5 November 2025
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	[[File:FISH 2.jpg\|thumb\|none\|link=Special:FilePath/FISH_2.jpg]]		[[File:FISH 2.jpg\|thumb\|none\|link=Special:FilePath/FISH_2.jpg]]
	[Concurrent abnormal karyotype with trisomy 21 and a translocation involving chromosomes X, 14, and 2 in 9 of 13 cells available for analysis; metaphase FISH with the ''IGH'' break-apart probe (Vysis) confirms the presence of 5’ ''IGH'' (green signal) on the abnormal chromosome Xp33.1 (''CRLF2'' locus), highly suggestive on an ''IGH''::''CRLF2'' fusion rearrangement: 47,XX,+21c[4]/47,idem,der(X)t(X;14)(p33.1;q32),der(2)t(2;14)(p11.2;q11.2)t(X;14),der(14)t(2;14)[5]/46,XX[4].ish der(X)(5’IGH+),der(2)(3’IGH+)]

	[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+)]		[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+)]

Mark.Evans: Entry completed

2025-11-05T22:34:30Z

Entry completed

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