HAEM5:B lymphoblastic leukaemia/lymphoma with TCF3::HLF fusion - Revision history

Aiko.Otsubo: /* Additional Information */

2025-11-11T18:55:55Z

Additional Information

← Older revision		Revision as of 13:55, 11 November 2025
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	==Additional Information==		==Additional Information==
	~~Put your text here~~		Not applicable.
	==Links==		==Links==

Aiko.Otsubo: /* Gene Mutations (SNV/INDEL) */

2025-11-11T18:53:36Z

Gene Mutations (SNV/INDEL)

← Older revision		Revision as of 13:53, 11 November 2025
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	==Individual Region Genomic Gain/Loss/LOH==		==Individual Region Genomic Gain/Loss/LOH==
	Deletions of PAX5, BTG1, and VPREB1 have been observed in TCF3::HLF-positive B-ALL. Of the 13 reported cases<ref>{{Cite journal\|last=Ma\|first=Xiaotu\|last2=Edmonson\|first2=Michael\|last3=Yergeau\|first3=Donald\|last4=Muzny\|first4=Donna M.\|last5=Hampton\|first5=Oliver A.\|last6=Rusch\|first6=Michael\|last7=Song\|first7=Guangchun\|last8=Easton\|first8=John\|last9=Harvey\|first9=Richard C.\|date=2015-03-19\|title=Rise and fall of subclones from diagnosis to relapse in pediatric B-acute lymphoblastic leukaemia\|url=https://pubmed.ncbi.nlm.nih.gov/25790293\|journal=Nature Communications\|volume=6\|pages=6604\|doi=10.1038/ncomms7604\|issn=2041-1723\|pmc=4377644\|pmid=25790293}}</ref><ref name=":0">{{Cite journal\|last=Fischer\|first=Ute\|last2=Forster\|first2=Michael\|last3=Rinaldi\|first3=Anna\|last4=Risch\|first4=Thomas\|last5=Sungalee\|first5=Stéphanie\|last6=Warnatz\|first6=Hans-Jörg\|last7=Bornhauser\|first7=Beat\|last8=Gombert\|first8=Michael\|last9=Kratsch\|first9=Christina\|date=2015-09\|title=Genomics and drug profiling of fatal TCF3-HLF-positive acute lymphoblastic leukemia identifies recurrent mutation patterns and therapeutic options\|url=https://pubmed.ncbi.nlm.nih.gov/26214592\|journal=Nature Genetics\|volume=47\|issue=9\|pages=1020–1029\|doi=10.1038/ng.3362\|issn=1546-1718\|pmc=4603357\|pmid=26214592}}</ref>, 8 showed deletions of PAX5. The remaining cases had deletions of BTG1, VPREB1, or both, but not PAX5, indicating deletions of PAX5 are mutually exclusive from deletions of BTG1 and VPREB1. CDKN2A/B deletions have been observed in 3 cases.		Deletions of PAX5, BTG1, and VPREB1 have been observed in TCF3::HLF-positive B-ALL. Of the 13 reported cases<ref name=":1">{{Cite journal\|last=Ma\|first=Xiaotu\|last2=Edmonson\|first2=Michael\|last3=Yergeau\|first3=Donald\|last4=Muzny\|first4=Donna M.\|last5=Hampton\|first5=Oliver A.\|last6=Rusch\|first6=Michael\|last7=Song\|first7=Guangchun\|last8=Easton\|first8=John\|last9=Harvey\|first9=Richard C.\|date=2015-03-19\|title=Rise and fall of subclones from diagnosis to relapse in pediatric B-acute lymphoblastic leukaemia\|url=https://pubmed.ncbi.nlm.nih.gov/25790293\|journal=Nature Communications\|volume=6\|pages=6604\|doi=10.1038/ncomms7604\|issn=2041-1723\|pmc=4377644\|pmid=25790293}}</ref><ref name=":0">{{Cite journal\|last=Fischer\|first=Ute\|last2=Forster\|first2=Michael\|last3=Rinaldi\|first3=Anna\|last4=Risch\|first4=Thomas\|last5=Sungalee\|first5=Stéphanie\|last6=Warnatz\|first6=Hans-Jörg\|last7=Bornhauser\|first7=Beat\|last8=Gombert\|first8=Michael\|last9=Kratsch\|first9=Christina\|date=2015-09\|title=Genomics and drug profiling of fatal TCF3-HLF-positive acute lymphoblastic leukemia identifies recurrent mutation patterns and therapeutic options\|url=https://pubmed.ncbi.nlm.nih.gov/26214592\|journal=Nature Genetics\|volume=47\|issue=9\|pages=1020–1029\|doi=10.1038/ng.3362\|issn=1546-1718\|pmc=4603357\|pmid=26214592}}</ref>, 8 showed deletions of PAX5. The remaining cases had deletions of BTG1, VPREB1, or both, but not PAX5, indicating deletions of PAX5 are mutually exclusive from deletions of BTG1 and VPREB1. CDKN2A/B deletions have been observed in 3 cases.
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	==Gene Mutations (SNV/INDEL)==		==Gene Mutations (SNV/INDEL)==
	RAS pathway gene alterations were identified in several TCF3::HLF-positive B-ALL cases. <span style="color:#0070C0">(''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.'') </span>		RAS pathway gene alterations were identified in several TCF3::HLF-positive B-ALL cases<ref name=":1" /><ref name=":0" />. <span style="color:#0070C0">(''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.'') </span>
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	\|Oncogene		\|Oncogene
	\|3/13 cases		\|3/13 cases
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Aiko.Otsubo: /* Gene Mutations (SNV/INDEL) */

2025-11-11T18:27:31Z

Gene Mutations (SNV/INDEL)

← Older revision		Revision as of 13:27, 11 November 2025
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	==Gene Mutations (SNV/INDEL)==		==Gene Mutations (SNV/INDEL)==
	~~Put your text here and fill~~ in ~~the table~~ <span style="color:#0070C0">(''Instructions: This table is not meant to be an exhaustive list; please include only genes/alterations that are recurrent 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.'') </span>		RAS pathway gene alterations were identified in several TCF3::HLF-positive B-ALL cases. <span style="color:#0070C0">(''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.'') </span>
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	Not applicable.		Not applicable.
	==Genes and Main Pathways Involved==		==Genes and Main Pathways Involved==
	TCF3 and HLF are both transcription factors, and their fusion generates a chimeric protein that combines the amino-terminal transactivation domains of TCF3 with the carboxy-terminal basic region/leucine zipper DNA-binding and dimerization domain of HLF. The resulting TCF3::HLF fusion protein exhibits altered DNA-binding ~~specificity~~ compared with wild-type HLF<ref>{{Cite journal\|last=Hunger\|first=S. P.\|last2=Ohyashiki\|first2=K.\|last3=Toyama\|first3=K.\|last4=Cleary\|first4=M. L.\|date=1992-09\|title=Hlf, a novel hepatic bZIP protein, shows altered DNA-binding properties following fusion to E2A in t(17;19) acute lymphoblastic leukemia\|url=https://pubmed.ncbi.nlm.nih.gov/1516826\|journal=Genes & Development\|volume=6\|issue=9\|pages=1608–1620\|doi=10.1101/gad.6.9.1608\|issn=0890-9369\|pmid=1516826}}</ref>. Functional studies have demonstrated that TCF3::HLF promotes anchorage-independent growth in mouse fibroblast cells<ref>{{Cite journal\|last=Yoshihara\|first=T.\|last2=Inaba\|first2=T.\|last3=Shapiro\|first3=L. H.\|last4=Kato\|first4=J. Y.\|last5=Look\|first5=A. T.\|date=1995-06\|title=E2A-HLF-mediated cell transformation requires both the trans-activation domains of E2A and the leucine zipper dimerization domain of HLF\|url=https://pubmed.ncbi.nlm.nih.gov/7760820\|journal=Molecular and Cellular Biology\|volume=15\|issue=6\|pages=3247–3255\|doi=10.1128/MCB.15.6.3247\|issn=0270-7306\|pmc=230557\|pmid=7760820}}</ref><ref>{{Cite journal\|last=Inukai\|first=T.\|last2=Inaba\|first2=T.\|last3=Yoshihara\|first3=T.\|last4=Look\|first4=A. T.\|date=1997-03\|title=Cell transformation mediated by homodimeric E2A-HLF transcription factors\|url=https://pubmed.ncbi.nlm.nih.gov/9032268\|journal=Molecular and Cellular Biology\|volume=17\|issue=3\|pages=1417–1424\|doi=10.1128/MCB.17.3.1417\|issn=0270-7306\|pmc=231866\|pmid=9032268}}</ref> and inhibits apoptosis, thereby enhancing cell survival<ref>{{Cite journal\|last=Inaba\|first=T.\|last2=Inukai\|first2=T.\|last3=Yoshihara\|first3=T.\|last4=Seyschab\|first4=H.\|last5=Ashmun\|first5=R. A.\|last6=Canman\|first6=C. E.\|last7=Laken\|first7=S. J.\|last8=Kastan\|first8=M. B.\|last9=Look\|first9=A. T.\|date=1996-08-08\|title=Reversal of apoptosis by the leukaemia-associated E2A-HLF chimaeric transcription factor\|url=https://pubmed.ncbi.nlm.nih.gov/8700228\|journal=Nature\|volume=382\|issue=6591\|pages=541–544\|doi=10.1038/382541a0\|issn=0028-0836\|pmid=8700228}}</ref><ref>{{Cite journal\|last=Inukai\|first=T.\|last2=Inaba\|first2=T.\|last3=Ikushima\|first3=S.\|last4=Look\|first4=A. T.\|date=1998-10\|title=The AD1 and AD2 transactivation domains of E2A are essential for the antiapoptotic activity of the chimeric oncoprotein E2A-HLF\|url=https://pubmed.ncbi.nlm.nih.gov/9742120\|journal=Molecular and Cellular Biology\|volume=18\|issue=10\|pages=6035–6043\|doi=10.1128/MCB.18.10.6035\|issn=0270-7306\|pmc=109189\|pmid=9742120}}</ref>. Gene expression profiling of TCF3::HLF-positive B-ALL cases further revealed extensive transcriptional reprogramming toward an aberrant, immature hematopoietic state<ref name=":0" />. <span style="color:#0070C0">(''Instructions: Please include references throughout the table. Do not delete the table.)''</span>		TCF3 and HLF are both transcription factors, and their fusion generates a chimeric protein that combines the amino-terminal transactivation domains of TCF3 with the carboxy-terminal basic region/leucine zipper DNA-binding and dimerization domain of HLF. The resulting TCF3::HLF fusion protein exhibits altered DNA-binding property compared with wild-type HLF<ref>{{Cite journal\|last=Hunger\|first=S. P.\|last2=Ohyashiki\|first2=K.\|last3=Toyama\|first3=K.\|last4=Cleary\|first4=M. L.\|date=1992-09\|title=Hlf, a novel hepatic bZIP protein, shows altered DNA-binding properties following fusion to E2A in t(17;19) acute lymphoblastic leukemia\|url=https://pubmed.ncbi.nlm.nih.gov/1516826\|journal=Genes & Development\|volume=6\|issue=9\|pages=1608–1620\|doi=10.1101/gad.6.9.1608\|issn=0890-9369\|pmid=1516826}}</ref>. Functional studies have demonstrated that TCF3::HLF promotes anchorage-independent growth in mouse fibroblast cells<ref>{{Cite journal\|last=Yoshihara\|first=T.\|last2=Inaba\|first2=T.\|last3=Shapiro\|first3=L. H.\|last4=Kato\|first4=J. Y.\|last5=Look\|first5=A. T.\|date=1995-06\|title=E2A-HLF-mediated cell transformation requires both the trans-activation domains of E2A and the leucine zipper dimerization domain of HLF\|url=https://pubmed.ncbi.nlm.nih.gov/7760820\|journal=Molecular and Cellular Biology\|volume=15\|issue=6\|pages=3247–3255\|doi=10.1128/MCB.15.6.3247\|issn=0270-7306\|pmc=230557\|pmid=7760820}}</ref><ref>{{Cite journal\|last=Inukai\|first=T.\|last2=Inaba\|first2=T.\|last3=Yoshihara\|first3=T.\|last4=Look\|first4=A. T.\|date=1997-03\|title=Cell transformation mediated by homodimeric E2A-HLF transcription factors\|url=https://pubmed.ncbi.nlm.nih.gov/9032268\|journal=Molecular and Cellular Biology\|volume=17\|issue=3\|pages=1417–1424\|doi=10.1128/MCB.17.3.1417\|issn=0270-7306\|pmc=231866\|pmid=9032268}}</ref> and inhibits apoptosis, thereby enhancing cell survival<ref>{{Cite journal\|last=Inaba\|first=T.\|last2=Inukai\|first2=T.\|last3=Yoshihara\|first3=T.\|last4=Seyschab\|first4=H.\|last5=Ashmun\|first5=R. A.\|last6=Canman\|first6=C. E.\|last7=Laken\|first7=S. J.\|last8=Kastan\|first8=M. B.\|last9=Look\|first9=A. T.\|date=1996-08-08\|title=Reversal of apoptosis by the leukaemia-associated E2A-HLF chimaeric transcription factor\|url=https://pubmed.ncbi.nlm.nih.gov/8700228\|journal=Nature\|volume=382\|issue=6591\|pages=541–544\|doi=10.1038/382541a0\|issn=0028-0836\|pmid=8700228}}</ref><ref>{{Cite journal\|last=Inukai\|first=T.\|last2=Inaba\|first2=T.\|last3=Ikushima\|first3=S.\|last4=Look\|first4=A. T.\|date=1998-10\|title=The AD1 and AD2 transactivation domains of E2A are essential for the antiapoptotic activity of the chimeric oncoprotein E2A-HLF\|url=https://pubmed.ncbi.nlm.nih.gov/9742120\|journal=Molecular and Cellular Biology\|volume=18\|issue=10\|pages=6035–6043\|doi=10.1128/MCB.18.10.6035\|issn=0270-7306\|pmc=109189\|pmid=9742120}}</ref>. Gene expression profiling of TCF3::HLF-positive B-ALL cases further revealed extensive transcriptional reprogramming toward an aberrant, immature hematopoietic state<ref name=":0" />. <span style="color:#0070C0">(''Instructions: Please include references throughout the table. Do not delete the table.)''</span>
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Aiko.Otsubo: /* Gene Mutations (SNV/INDEL) */

2025-11-11T18:19:19Z

Gene Mutations (SNV/INDEL)

← Older revision		Revision as of 13:19, 11 November 2025
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	\|~~<span class="blue-text">EXAMPLE:</span>~~ ''~~TP53KRAS~~''~~; Variable LOF mutationsKRAS~~		\|''KRAS''<br />
	<br />
	\|Activating mutations		\|Activating mutations
	\|Oncogene		\|Oncogene
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	\|~~<span class="blue-text">EXAMPLE:</span>~~ ''~~BRAF~~''~~; Activating mutations~~		\|''PTPN11''
	\|~~<span class="blue-text">EXAMPLE:</span>~~ Activating mutations		\|Activating mutations
	\|~~<span class="blue-text">EXAMPLE:</span>~~ Oncogene		\|Oncogene
	\|~~<span class="blue-text">EXAMPLE:<~~/~~span> Common (melanoma)~~		\|3/13 cases
	\|~~<span class="blue-text">EXAMPLE:</span> T~~		\|
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Aiko.Otsubo: /* Gene Mutations (SNV/INDEL) */

2025-11-11T18:17:41Z

Gene Mutations (SNV/INDEL)

← Older revision		Revision as of 13:17, 11 November 2025
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	!Clinical Relevance Details/Other Notes		!Clinical Relevance Details/Other Notes
	\|-		\|-
	\|~~<span class="blue-text">EXAMPLE:</span>~~''~~EGFR~~''		\|''NRAS''

	<br />		<br />
	\|~~<span class="blue-text">EXAMPLE:</span> Exon 18-21 activating~~ mutations		\|Activating mutations
	\|~~<span class="blue-text">EXAMPLE:</span>~~ Oncogene		\|Oncogene
	\|~~<span class="blue-text">EXAMPLE:<~~/~~span> Common (lung cancer)~~		\|3/13 cases
	\|~~<span class="blue-text">EXAMPLE:</span> T~~		\|
	\|~~<span class="blue-text">EXAMPLE:</span> Yes (NCCN)~~		\|
	\|<span class="blue-text">EXAMPLE:</span> 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).		\|
	\|-		\|-
	\|<span class="blue-text">EXAMPLE:</span> ''~~TP53~~''; Variable LOF ~~mutations~~		\|<span class="blue-text">EXAMPLE:</span> ''TP53KRAS''; Variable LOF mutationsKRAS
	<br />		<br />
	\|~~<span class="blue-text">EXAMPLE:</span> Variable LOF~~ mutations		\|Activating mutations
	\|~~<span class="blue-text">EXAMPLE:<~~/~~span> Tumor Supressor Gene~~		\|Oncogene
	\|~~<span class="blue-text">EXAMPLE:</span> Common (breast cancer)~~		\|3/13 cases
	\|~~<span class="blue-text">EXAMPLE:</span> P~~		\|
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	~~\|<span class="blue-text">EXAMPLE:</span> >90% are somatic; rare germline alterations associated with Li-Fraumeni syndrome (add reference). Denotes a poor prognosis in breast cancer.~~
	\|-		\|-
	\|<span class="blue-text">EXAMPLE:</span> ''BRAF''; Activating mutations		\|<span class="blue-text">EXAMPLE:</span> ''BRAF''; Activating mutations

Aiko.Otsubo: /* Genes and Main Pathways Involved */

2025-11-11T18:12:32Z

Genes and Main Pathways Involved

← Older revision		Revision as of 13:12, 11 November 2025
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	!Clinical Relevance Details/Other Notes		!Clinical Relevance Details/Other Notes
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	\|''TCF3''\|\|''TCF3 (E2A)::HLF''\|\|The pathogenic derivative is the der(19) resulting in fusion of 5’ TCF3 and 3’HLF.\|\|t(17;19)(q22;p13)		\|''TCF3 and HLF''\|\|''TCF3 (E2A)::HLF''\|\|The pathogenic derivative is the der(19) resulting in fusion of 5’ TCF3 and 3’HLF.\|\|t(17;19)(q22;p13)
	\|Rare		\|Rare
	\|D, P		\|D, P
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	!Gene; Genetic Alteration!!Pathway!!Pathophysiologic Outcome		!Gene; Genetic Alteration!!Pathway!!Pathophysiologic Outcome
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	\|~~<span class="blue-text">EXAMPLE:</span> ''BRAF~~'' and ''~~MAP2K1''; Activating mutations~~		\|''TCF3 and HLF''
	\|~~<span class="blue-text">EXAMPLE:</span> MAPK signaling~~		\|Lymphoid differentiation
	\|~~<span class="blue-text">EXAMPLE:</span> Increased cell growth and proliferation~~		\|Abnormal gene expression
	\|-		\|-
	\|<span class="blue-text">EXAMPLE:</span> ''CDKN2A''; Inactivating mutations		\|<span class="blue-text">EXAMPLE:</span> ''CDKN2A''; Inactivating mutations

Aiko.Otsubo: /* Links */

2025-11-11T18:04:18Z

Links

← Older revision		Revision as of 13:04, 11 November 2025
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	[[TCF3]]		[[TCF3]]

	[[HLF]]		HLF

	<span style="color:#0070C0">(''Instructions: Highlight the text to which you want to add a link in this section or elsewhere, select the "Link" icon at the top of the wiki page, and search the name of the internal page to which you want to link this text, or enter an external internet address by including the "<nowiki>http://www</nowiki>." portion.'')</span>		<span style="color:#0070C0">(''Instructions: Highlight the text to which you want to add a link in this section or elsewhere, select the "Link" icon at the top of the wiki page, and search the name of the internal page to which you want to link this text, or enter an external internet address by including the "<nowiki>http://www</nowiki>." portion.'')</span>

Aiko.Otsubo: /* Links */

2025-11-11T18:03:39Z

Links

← Older revision		Revision as of 13:03, 11 November 2025
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	==Links==		==Links==

	~~Put a link here or anywhere appropriate in this page~~ <span style="color:#0070C0">(''Instructions: Highlight the text to which you want to add a link in this section or elsewhere, select the "Link" icon at the top of the wiki page, and search the name of the internal page to which you want to link this text, or enter an external internet address by including the "<nowiki>http://www</nowiki>." portion.'')</span>		[[TCF3]]

			[[HLF]]

			<span style="color:#0070C0">(''Instructions: Highlight the text to which you want to add a link in this section or elsewhere, select the "Link" icon at the top of the wiki page, and search the name of the internal page to which you want to link this text, or enter an external internet address by including the "<nowiki>http://www</nowiki>." portion.'')</span>

	==References==		==References==

Aiko.Otsubo: /* Genetic Diagnostic Testing Methods */

2025-11-11T18:01:25Z

Genetic Diagnostic Testing Methods

← Older revision		Revision as of 13:01, 11 November 2025
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	==Genetic Diagnostic Testing Methods==		==Genetic Diagnostic Testing Methods==
	~~Put your text here <span style="color:#0070C0">(''Instructions: Include recommended testing type(s) to identify the clinically significant genetic alterations.'')</span>~~		Karyotype, FISH, RT-PCR, DNA or RNA-based NGS

	==Familial Forms==		==Familial Forms==
	Not applicable.		Not applicable.

Aiko.Otsubo: /* Gene Mutations (SNV/INDEL) */

2025-11-11T18:00:35Z

Gene Mutations (SNV/INDEL)

← Older revision		Revision as of 13:00, 11 November 2025
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	==Gene Rearrangements==		==Gene Rearrangements==
	B lymphoblastic leukaemia/lymphoma (B-ALL) with t(17;19)(q22;p13), resulting in the TCF3::HLF gene fusion, is newly recognized as a distinct entity in the WHO 5th edition classification. TCF3 rearrangements are identified in approximately 5–11% of B-ALL cases, with several fusion partners reported, including PBX1, HLF, and ZNF384. B-ALL with TCF3::PBX1 fusion is also classified as a separate entity in the latest WHO edition<ref>WHO Classification of Tumours Editorial Board, eds, WHO Classification of Tumours, Haematolymphoid Tumours, 5th edition, IARC Press:Lyon, 2024. Online at WHO Classification of Tumours</ref>. <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>		B lymphoblastic leukaemia/lymphoma (B-ALL) with t(17;19)(q22;p13), resulting in the TCF3::HLF gene fusion, is newly recognized as a distinct entity in the WHO 5th edition classification. TCF3 rearrangements are identified in approximately 5–11% of B-ALL cases, with several fusion partners reported, including PBX1, HLF, and ZNF384. B-ALL with TCF3::PBX1 fusion is also classified as a separate entity in the latest WHO edition<ref>WHO Classification of Tumours Editorial Board, eds, WHO Classification of Tumours, Haematolymphoid Tumours, 5th edition, IARC Press:Lyon, 2024. Online at WHO Classification of Tumours</ref>.
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	==Individual Region Genomic Gain/Loss/LOH==		==Individual Region Genomic Gain/Loss/LOH==
	Deletions of PAX5, BTG1, and VPREB1 have been observed in TCF3::HLF-positive B-ALL. Of the 13 reported cases<ref>{{Cite journal\|last=Ma\|first=Xiaotu\|last2=Edmonson\|first2=Michael\|last3=Yergeau\|first3=Donald\|last4=Muzny\|first4=Donna M.\|last5=Hampton\|first5=Oliver A.\|last6=Rusch\|first6=Michael\|last7=Song\|first7=Guangchun\|last8=Easton\|first8=John\|last9=Harvey\|first9=Richard C.\|date=2015-03-19\|title=Rise and fall of subclones from diagnosis to relapse in pediatric B-acute lymphoblastic leukaemia\|url=https://pubmed.ncbi.nlm.nih.gov/25790293\|journal=Nature Communications\|volume=6\|pages=6604\|doi=10.1038/ncomms7604\|issn=2041-1723\|pmc=4377644\|pmid=25790293}}</ref><ref>{{Cite journal\|last=Fischer\|first=Ute\|last2=Forster\|first2=Michael\|last3=Rinaldi\|first3=Anna\|last4=Risch\|first4=Thomas\|last5=Sungalee\|first5=Stéphanie\|last6=Warnatz\|first6=Hans-Jörg\|last7=Bornhauser\|first7=Beat\|last8=Gombert\|first8=Michael\|last9=Kratsch\|first9=Christina\|date=2015-09\|title=Genomics and drug profiling of fatal TCF3-HLF-positive acute lymphoblastic leukemia identifies recurrent mutation patterns and therapeutic options\|url=https://pubmed.ncbi.nlm.nih.gov/26214592\|journal=Nature Genetics\|volume=47\|issue=9\|pages=1020–1029\|doi=10.1038/ng.3362\|issn=1546-1718\|pmc=4603357\|pmid=26214592}}</ref>, 8 showed deletions of PAX5. The remaining cases had deletions of BTG1, VPREB1, or both, but not PAX5, indicating deletions of PAX5 are mutually exclusive from deletions of BTG1 and VPREB1. CDKN2A/B deletions have been observed in 3 cases.		Deletions of PAX5, BTG1, and VPREB1 have been observed in TCF3::HLF-positive B-ALL. Of the 13 reported cases<ref>{{Cite journal\|last=Ma\|first=Xiaotu\|last2=Edmonson\|first2=Michael\|last3=Yergeau\|first3=Donald\|last4=Muzny\|first4=Donna M.\|last5=Hampton\|first5=Oliver A.\|last6=Rusch\|first6=Michael\|last7=Song\|first7=Guangchun\|last8=Easton\|first8=John\|last9=Harvey\|first9=Richard C.\|date=2015-03-19\|title=Rise and fall of subclones from diagnosis to relapse in pediatric B-acute lymphoblastic leukaemia\|url=https://pubmed.ncbi.nlm.nih.gov/25790293\|journal=Nature Communications\|volume=6\|pages=6604\|doi=10.1038/ncomms7604\|issn=2041-1723\|pmc=4377644\|pmid=25790293}}</ref><ref name=":0">{{Cite journal\|last=Fischer\|first=Ute\|last2=Forster\|first2=Michael\|last3=Rinaldi\|first3=Anna\|last4=Risch\|first4=Thomas\|last5=Sungalee\|first5=Stéphanie\|last6=Warnatz\|first6=Hans-Jörg\|last7=Bornhauser\|first7=Beat\|last8=Gombert\|first8=Michael\|last9=Kratsch\|first9=Christina\|date=2015-09\|title=Genomics and drug profiling of fatal TCF3-HLF-positive acute lymphoblastic leukemia identifies recurrent mutation patterns and therapeutic options\|url=https://pubmed.ncbi.nlm.nih.gov/26214592\|journal=Nature Genetics\|volume=47\|issue=9\|pages=1020–1029\|doi=10.1038/ng.3362\|issn=1546-1718\|pmc=4603357\|pmid=26214592}}</ref>, 8 showed deletions of PAX5. The remaining cases had deletions of BTG1, VPREB1, or both, but not PAX5, indicating deletions of PAX5 are mutually exclusive from deletions of BTG1 and VPREB1. CDKN2A/B deletions have been observed in 3 cases.

	<span style="color:#0070C0">(''Instructions: Includes aberrations not involving gene rearrangements. Details on clinical significance such as prognosis and other important information can be provided in the notes section. Can refer to CGC workgroup tables as linked on the homepage if applicable. Please include references throughout the table. Do not delete the table.'') </span>
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	Not applicable.		Not applicable.
	==Genes and Main Pathways Involved==		==Genes and Main Pathways Involved==
	~~Put your text here~~ and ~~fill~~ in the ~~table~~ <span style="color:#0070C0">(''Instructions: Please include references throughout the table. Do not delete the table.)''</span>		TCF3 and HLF are both transcription factors, and their fusion generates a chimeric protein that combines the amino-terminal transactivation domains of TCF3 with the carboxy-terminal basic region/leucine zipper DNA-binding and dimerization domain of HLF. The resulting TCF3::HLF fusion protein exhibits altered DNA-binding specificity compared with wild-type HLF<ref>{{Cite journal\|last=Hunger\|first=S. P.\|last2=Ohyashiki\|first2=K.\|last3=Toyama\|first3=K.\|last4=Cleary\|first4=M. L.\|date=1992-09\|title=Hlf, a novel hepatic bZIP protein, shows altered DNA-binding properties following fusion to E2A in t(17;19) acute lymphoblastic leukemia\|url=https://pubmed.ncbi.nlm.nih.gov/1516826\|journal=Genes & Development\|volume=6\|issue=9\|pages=1608–1620\|doi=10.1101/gad.6.9.1608\|issn=0890-9369\|pmid=1516826}}</ref>. Functional studies have demonstrated that TCF3::HLF promotes anchorage-independent growth in mouse fibroblast cells<ref>{{Cite journal\|last=Yoshihara\|first=T.\|last2=Inaba\|first2=T.\|last3=Shapiro\|first3=L. H.\|last4=Kato\|first4=J. Y.\|last5=Look\|first5=A. T.\|date=1995-06\|title=E2A-HLF-mediated cell transformation requires both the trans-activation domains of E2A and the leucine zipper dimerization domain of HLF\|url=https://pubmed.ncbi.nlm.nih.gov/7760820\|journal=Molecular and Cellular Biology\|volume=15\|issue=6\|pages=3247–3255\|doi=10.1128/MCB.15.6.3247\|issn=0270-7306\|pmc=230557\|pmid=7760820}}</ref><ref>{{Cite journal\|last=Inukai\|first=T.\|last2=Inaba\|first2=T.\|last3=Yoshihara\|first3=T.\|last4=Look\|first4=A. T.\|date=1997-03\|title=Cell transformation mediated by homodimeric E2A-HLF transcription factors\|url=https://pubmed.ncbi.nlm.nih.gov/9032268\|journal=Molecular and Cellular Biology\|volume=17\|issue=3\|pages=1417–1424\|doi=10.1128/MCB.17.3.1417\|issn=0270-7306\|pmc=231866\|pmid=9032268}}</ref> and inhibits apoptosis, thereby enhancing cell survival<ref>{{Cite journal\|last=Inaba\|first=T.\|last2=Inukai\|first2=T.\|last3=Yoshihara\|first3=T.\|last4=Seyschab\|first4=H.\|last5=Ashmun\|first5=R. A.\|last6=Canman\|first6=C. E.\|last7=Laken\|first7=S. J.\|last8=Kastan\|first8=M. B.\|last9=Look\|first9=A. T.\|date=1996-08-08\|title=Reversal of apoptosis by the leukaemia-associated E2A-HLF chimaeric transcription factor\|url=https://pubmed.ncbi.nlm.nih.gov/8700228\|journal=Nature\|volume=382\|issue=6591\|pages=541–544\|doi=10.1038/382541a0\|issn=0028-0836\|pmid=8700228}}</ref><ref>{{Cite journal\|last=Inukai\|first=T.\|last2=Inaba\|first2=T.\|last3=Ikushima\|first3=S.\|last4=Look\|first4=A. T.\|date=1998-10\|title=The AD1 and AD2 transactivation domains of E2A are essential for the antiapoptotic activity of the chimeric oncoprotein E2A-HLF\|url=https://pubmed.ncbi.nlm.nih.gov/9742120\|journal=Molecular and Cellular Biology\|volume=18\|issue=10\|pages=6035–6043\|doi=10.1128/MCB.18.10.6035\|issn=0270-7306\|pmc=109189\|pmid=9742120}}</ref>. Gene expression profiling of TCF3::HLF-positive B-ALL cases further revealed extensive transcriptional reprogramming toward an aberrant, immature hematopoietic state<ref name=":0" />. <span style="color:#0070C0">(''Instructions: Please include references throughout the table. Do not delete the table.)''</span>
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