HAEM5:B lymphoblastic leukaemia/lymphoma with TCF3::HLF fusion: Difference between revisions

|''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)

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.

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>

|<span class="blue-text">EXAMPLE:</span>''EGFR''

|<span class="blue-text">EXAMPLE:</span> Exon 18-21 activating mutations

|<span class="blue-text">EXAMPLE:</span> Oncogene

|<span class="blue-text">EXAMPLE:</span> Common (lung cancer)

|<span class="blue-text">EXAMPLE:</span> P

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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>

|<span class="blue-text">EXAMPLE:</span> ''BRAF'' and ''MAP2K1''; Activating mutations

|<span class="blue-text">EXAMPLE:</span> MAPK signaling

|<span class="blue-text">EXAMPLE:</span> Increased cell growth and proliferation