HAEM5:B lymphoblastic leukaemia/lymphoma with TCF3::HLF fusion: Difference between revisions
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|Acceptable | |Acceptable | ||
|N/A | |N/A | ||
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==Gene Rearrangements== | ==Gene Rearrangements== | ||
{| class="wikitable sortable" | {| class="wikitable sortable" | ||
|- | |- | ||
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|D, P | |D, P | ||
|Yes (WHO, NCCN) | |Yes (WHO, NCCN) | ||
| | |1% of childhood B-ALL cases. Majority of cases are pediatric, but it has also been reported in adults<ref>{{Cite journal|last=Ahmed|first=Maria Z.|last2=Venkatadasari|first2=Indrani|last3=Dyer|first3=Sara|last4=Wall|first4=Kerry|last5=Huxley|first5=Emma|last6=Lovell|first6=Richard|last7=Kishore|first7=Bhuvan|last8=Dassanayake|first8=Hansini|last9=Francis|first9=Sebastian|date=2022-11|title=Clonal evolution in adult TCF3::HLF-positive acute lymphoblastic leukemia undergoing stem cell transplantation|url=https://pubmed.ncbi.nlm.nih.gov/35907039|journal=Annals of Hematology|volume=101|issue=11|pages=2553–2554|doi=10.1007/s00277-022-04941-5|issn=1432-0584|pmid=35907039}}</ref><ref>{{Cite journal|last=Zeckanovic|first=Aida|last2=Mouttet|first2=Brice|last3=Vinti|first3=Luciana|last4=Ancliff|first4=Philip|last5=Brethon|first5=Benoît|last6=Cario|first6=Gunnar|last7=Elitzur|first7=Sarah|last8=Hazar|first8=Volkan|last9=Kunz|first9=Joachim|date=2025-06-01|title=Update on long-term outcomes of a cohort of patients with TCF3::HLF-positive acute lymphoblastic leukemia treated with blinatumomab and stem cell transplantation|url=https://pubmed.ncbi.nlm.nih.gov/39911115|journal=Haematologica|volume=110|issue=6|pages=1373–1378|doi=10.3324/haematol.2024.286111|issn=1592-8721|pmc=12130763|pmid=39911115}}</ref> | ||
Two major types of ''TCF3''::''HLF'' gene fusion have been identified<ref>{{Cite journal|last=Hunger|first=S. P.|last2=Devaraj|first2=P. E.|last3=Foroni|first3=L.|last4=Secker-Walker|first4=L. M.|last5=Cleary|first5=M. L.|date=1994-05-15|title=Two types of genomic rearrangements create alternative E2A-HLF fusion proteins in t(17;19)-ALL|url=https://pubmed.ncbi.nlm.nih.gov/8180393|journal=Blood|volume=83|issue=10|pages=2970–2977|issn=0006-4971|pmid=8180393}}</ref><ref>{{Cite journal|last=Panagopoulos|first=Ioannis|last2=Micci|first2=Francesca|last3=Thorsen|first3=Jim|last4=Haugom|first4=Lisbeth|last5=Tierens|first5=Anne|last6=Ulvmoen|first6=Aina|last7=Heim|first7=Sverre|date=2012-12|title=A novel TCF3-HLF fusion transcript in acute lymphoblastic leukemia with a t(17;19)(q22;p13)|url=https://pubmed.ncbi.nlm.nih.gov/23181981|journal=Cancer Genetics|volume=205|issue=12|pages=669–672|doi=10.1016/j.cancergen.2012.10.004|issn=2210-7762|pmid=23181981}}</ref><ref>{{Cite journal|last=Lejman|first=Monika|last2=Włodarczyk|first2=Monika|last3=Zawitkowska|first3=Joanna|last4=Kowalczyk|first4=Jerzy R.|date=2020-04-03|title=Comprehensive chromosomal aberrations in a case of a patient with TCF3-HLF-positive BCP-ALL|url=https://pubmed.ncbi.nlm.nih.gov/32245383|journal=BMC medical genomics|volume=13|issue=1|pages=58|doi=10.1186/s12920-020-0709-y|issn=1755-8794|pmc=7118981|pmid=32245383}}</ref>. | |||
* Type 1: ''TCF3'' (NM_003200.3) exon 16 fused to ''HLF'' (NM_002126.4) exon 4 | |||
* Type 2: ''TCF3'' exon 15 fused to ''HLF'' exon 4 | |||
Extremely poor prognosis, high resistance to conventional therapy, and early relapse | |||
Frequently accompanied by disseminated intravascular coagulation (DIC) and hypercalcemia<ref>{{Cite journal|last=Hunger|first=S. P.|date=1996-02-15|title=Chromosomal translocations involving the E2A gene in acute lymphoblastic leukemia: clinical features and molecular pathogenesis|url=https://pubmed.ncbi.nlm.nih.gov/8608207|journal=Blood|volume=87|issue=4|pages=1211–1224|issn=0006-4971|pmid=8608207}}</ref><ref>{{Cite journal|last=Matsunaga|first=Takayuki|last2=Inaba|first2=Toshiya|last3=Matsui|first3=Hirotaka|last4=Okuya|first4=Mayuko|last5=Miyajima|first5=Atsushi|last6=Inukai|first6=Takeshi|last7=Funabiki|first7=Tetsunori|last8=Endo|first8=Mikiya|last9=Look|first9=A. Thomas|date=2004-04-15|title=Regulation of annexin II by cytokine-initiated signaling pathways and E2A-HLF oncoprotein|url=https://pubmed.ncbi.nlm.nih.gov/15070701|journal=Blood|volume=103|issue=8|pages=3185–3191|doi=10.1182/blood-2003-09-3022|issn=0006-4971|pmid=15070701}}</ref><ref>{{Cite journal|last=Minson|first=Katherine A.|last2=Prasad|first2=Pinki|last3=Vear|first3=Susan|last4=Borinstein|first4=Scott|last5=Ho|first5=Richard|last6=Domm|first6=Jennifer|last7=Frangoul|first7=Haydar|date=2013|title=t(17;19) in Children with Acute Lymphocytic Leukemia: A Report of 3 Cases and a Review of the Literature|url=https://pubmed.ncbi.nlm.nih.gov/23346431|journal=Case Reports in Hematology|volume=2013|pages=563291|doi=10.1155/2013/563291|issn=2090-6560|pmc=3549381|pmid=23346431}}</ref><ref>{{Cite journal|last=Inukai|first=T.|last2=Hirose|first2=K.|last3=Inaba|first3=T.|last4=Kurosawa|first4=H.|last5=Hama|first5=A.|last6=Inada|first6=H.|last7=Chin|first7=M.|last8=Nagatoshi|first8=Y.|last9=Ohtsuka|first9=Y.|date=2007-02|title=Hypercalcemia in childhood acute lymphoblastic leukemia: frequent implication of parathyroid hormone-related peptide and E2A-HLF from translocation 17;19|url=https://pubmed.ncbi.nlm.nih.gov/17183364|journal=Leukemia|volume=21|issue=2|pages=288–296|doi=10.1038/sj.leu.2404496|issn=0887-6924|pmid=17183364}}</ref>. | |||
|} | |} | ||
''TCF3'' rearrangements are identified in approximately 5–11% of B-ALL cases. Other fusion partners reported include ''PBX1'' and ''ZNF384'' where B-ALL with ''TCF3''::''PBX1'' fusion is classified as a separate, distinct 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>. | |||
==Individual Region Genomic Gain/Loss/LOH== | ==Individual Region Genomic Gain/Loss/LOH== | ||
Of 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 were observed in 3 cases. | Of 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 were observed in 3 cases. | ||
| Line 73: | Line 76: | ||
|9p13 | |9p13 | ||
|''PAX5'' | |''PAX5'' | ||
| | |NA | ||
|No | |No | ||
|Common recurrent finding in B-ALL; may be mutually exclusive from deletions of ''BTG1'' and ''VPREB1'' | |Common recurrent finding in B-ALL; may be mutually exclusive from deletions of ''BTG1'' and ''VPREB1'' | ||
| Line 81: | Line 84: | ||
|9p21.3 | |9p21.3 | ||
|''CDKN2A/B'' | |''CDKN2A/B'' | ||
| | |NA | ||
|No | |No | ||
|Common recurrent finding in various cancers | |Common recurrent finding in various cancers | ||
| Line 89: | Line 92: | ||
|12q21.33 | |12q21.33 | ||
|''BTG1'' | |''BTG1'' | ||
| | |NA | ||
|No | |No | ||
|Common recurrent finding in B-ALL; may co-occur with deletion of ''VPREB1''; may be mutually exclusive from deletions of ''PAX5'' | |Common recurrent finding in B-ALL; may co-occur with deletion of ''VPREB1''; may be mutually exclusive from deletions of ''PAX5'' | ||
| Line 97: | Line 100: | ||
|22q11.2 | |22q11.2 | ||
|''VPREB1'' | |''VPREB1'' | ||
| | |NA | ||
|No | |No | ||
|Common recurrent finding in B-ALL; may co-occur with deletion of ''BTG1''; may be mutually exclusive from deletions of ''PAX5'' | |Common recurrent finding in B-ALL; may co-occur with deletion of ''BTG1''; may be mutually exclusive from deletions of ''PAX5'' | ||
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|} | |} | ||
==Gene Mutations (SNV/INDEL)== | ==Gene Mutations (SNV/INDEL)== | ||
''RAS'' pathway gene alterations were | ''RAS'' pathway gene alterations were common in ''TCF3''::''HLF''-positive B-ALL cases<ref name=":1" /><ref name=":0" />. | ||
{| class="wikitable sortable" | {| class="wikitable sortable" | ||
|- | |- | ||
| Line 133: | Line 136: | ||
|Activating mutations | |Activating mutations | ||
|Oncogene | |Oncogene | ||
| | |Common | ||
| | |NA | ||
|No | |No | ||
| | |Treatment potential with MAPK/MEK inhibitors | ||
|- | |- | ||
|''KRAS''<br /> | |''KRAS''<br /> | ||
|Activating mutations | |Activating mutations | ||
|Oncogene | |Oncogene | ||
| | |Recurrent | ||
| | |NA | ||
|No | |No | ||
| | |Treatment potential with MAPK/MEK inhibitors | ||
|- | |- | ||
|''PTPN11'' | |''PTPN11'' | ||
| | |Gain of function | ||
|Oncogene | |Oncogene | ||
| | |Recurrent | ||
| | |NA | ||
|No | |No | ||
| | |Treatment potential with MAPK/MEK inhibitors | ||
|}Note: A more extensive list of mutations can be found in [https://www.cbioportal.org/ <u>cBioportal</u>], [https://cancer.sanger.ac.uk/cosmic <u>COSMIC</u>], and/or other databases. When applicable, gene-specific pages within the CCGA site directly link to pertinent external content. | |}Note: A more extensive list of mutations can be found in [https://www.cbioportal.org/ <u>cBioportal</u>], [https://cancer.sanger.ac.uk/cosmic <u>COSMIC</u>], and/or other databases. When applicable, gene-specific pages within the CCGA site directly link to pertinent external content. | ||
==Epigenomic Alterations== | ==Epigenomic Alterations== | ||
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[[TCF3]] | [[TCF3]] | ||
==References== | ==References== | ||