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

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

2025-11-06T21:08:54Z

Primary Author(s)*

← Older revision		Revision as of 16:08, 6 November 2025
Line 12:		Line 12:
	==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
Line 711:		Line 711:
	\|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
Line 679:		Line 679:
	\|''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
Line 64:		Line 64:
	\|'''Comment'''		\|'''Comment'''
	\|-		\|-
	\| rowspan="12" \|~~'''~~''[[ABL1]]~~'''~~''		\| rowspan="12" \|''[[ABL1]]''
	(9q34)		(9q34)
	\|''CENPC1''		\|''CENPC1''
Line 150:		Line 150:
	\|		\|
	\|-		\|-
	\| rowspan="3" \|~~'''~~''[[ABL2]]~~'''~~''		\| rowspan="3" \|''[[ABL2]]''
	(1q25.2)		(1q25.2)
	\|''PAG1''		\|''PAG1''
Line 173:		Line 173:
	\|		\|
	\|-		\|-
	\| rowspan="2" \|~~'''~~''[[CRLF2]]~~'''~~''		\| rowspan="2" \|''[[CRLF2]]''
	(Xp22.3 & Yp11.3)		(Xp22.3 & Yp11.3)
	\|''[[IGH]]''		\|''[[IGH]]''
Line 190:		Line 190:
	\|		\|
	\|-		\|-
	\| rowspan="3" \|~~'''~~''CSF1R~~'''~~''		\| rowspan="3" \|''CSF1R''
	(5q32)		(5q32)
	\|''MEF2D''		\|''MEF2D''
Line 213:		Line 213:
	\|		\|
	\|-		\|-
	\|~~'''~~''DGKH~~'''~~'' (13q14.1)		\|''DGKH'' (13q14.1)
	\|''ZFAND3''		\|''ZFAND3''
	\|t(6;13)(p21.2;q14.1)		\|t(6;13)(p21.2;q14.1)
Line 221:		Line 221:
	\|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)
Line 250:		Line 250:
	\|		\|
	\|-		\|-
	\|~~'''~~''IL2RB~~'''~~'' (22q12.3)		\|''IL2RB'' (22q12.3)
	\|''MYH9''		\|''MYH9''
	\|22q12.3 rearrangement		\|22q12.3 rearrangement
Line 258:		Line 258:
	\|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''
Line 414:		Line 414:
	\|		\|
	\|-		\|-
	\|~~'''~~''[[PDGFRA]]~~'''~~''		\|''[[PDGFRA]]''
	(4q12)		(4q12)
	\|''FIP1L1''		\|''FIP1L1''
Line 423:		Line 423:
	\|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)
Line 480:		Line 480:
	\|		\|
	\|-		\|-
	\| 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)
Line 502:		Line 502:
	\|		\|
	\|-		\|-
	\| 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
Line 667:		Line 667:
	\|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
Line 677:		Line 677:
	\|''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
Line 633:		Line 633:

	[[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

Show changes

Mark.Evans at 22:22, 5 November 2025

2025-11-05T22:22:50Z

Show changes

Mark.Evans at 18:43, 5 November 2025

2025-11-05T18:43:13Z

← Older revision		Revision as of 13:43, 5 November 2025
Line 619:		Line 619:
	\|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>		\|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>
	\|-		\|-
	\|~~Extra~~ or iAMP21		\|Polysomy or iAMP21
	\|These changes stem from telomere attrition that result in the amplification of all or a region on chromosome 21.		\|These changes stem from telomere attrition that result in the amplification of all or a region on chromosome 21.
	\|Rare (<5%)		\|Rare (<5%)