HAEM5:B lymphoblastic leukaemia/lymphoma with TCF3::PBX1 fusion: Difference between revisions

No unique clinical features that distinguish this entity from other types of B-ALL. Common clinical features of B-ALL include:

These features manifest clinically as anemia, neutropenia, and/or thrombocytopenia. <ref name=":0" />

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==Sites of Involvement==

Blasts with pre-B phenotype, positive for CD19, CD10 and cytoplasmic mu heavy chain. <ref name=":1" />

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==Chromosomal Rearrangements (Gene Fusions)==

The breakpoints of the t(1;19) translocation  typically fall within intron 16 of ''TCF3'' and intron 3 of ''PBX1''. <ref name=":0" />

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* Individual Region Genomic Gain/Loss/LOH

* Characteristic Chromosomal Patterns

The t(1;19) diagnosis was associated with high risk and poor prognosis in earlier studies, however, modern intensive chemotherapy has changed this paradigm. A recent (2021) study showed that patients with ''TCF3-PBX1'' had intermediate rates of 5-year event-free survival (80-88.2%). Despite the favorable prognosis of this subtype of ALL, there is an increased relative risk of central nervous system relapse associated with this translocation.  <ref name=":1" /><ref name=":0" /><ref>{{Cite journal|last=Jeha|first=Sima|last2=Choi|first2=John|last3=Roberts|first3=Kathryn G.|last4=Pei|first4=Deqing|last5=Coustan-Smith|first5=Elaine|last6=Inaba|first6=Hiroto|last7=Rubnitz|first7=Jeffrey E.|last8=Ribeiro|first8=Raul C.|last9=Gruber|first9=Tanja A.|date=2021-07|title=Clinical significance of novel subtypes of acute lymphoblastic leukemia in the context of minimal residual disease-directed therapy|url=https://pubmed.ncbi.nlm.nih.gov/34250504|journal=Blood Cancer Discovery|volume=2|issue=4|pages=326–337|doi=10.1158/2643-3230.bcd-20-0229|issn=2643-3249|pmc=8265990|pmid=34250504}}</ref>

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==Individual Region Genomic Gain / Loss / LOH==

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Secondary somatic copy number aberrations are not frequently seen in ''TCF3-PBX1'' B-ALL

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==Characteristic Chromosomal Patterns==

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The t(1;19) translocation can be balanced or unbalanced. The unbalanced form has a der(19) resulting in trisomy of 1q distal to PBX1.<ref name=":2">Meloni-Ehrig A., (2013). The principles of clinical cytogenetics. 3rd edition. Steven L. Gersen and Martha B. Keagle , Editors. Springer. DOI 10.1007/978-1-4419-1688-4. p327-329.</ref>  

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==Gene Mutations (SNV / INDEL)==

Secondary somatic DNA mutations are not frequently seen in ''TCF3-PBX1'' B-ALL. <ref name=":0" />

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==Epigenomic Alterations==

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''TCF3'' gene at 19p13.3 is important during early lymphocyte development, whereas ''PBX1'' at 1q23 is a component of a transcriptional complex that regulates embryogenesis and hematopoiesis. Fusion protein resulting from the TCF3-PBX1 translocation is a transcriptional activator which likely interferes with the normal function of these genes. Expression of this fusion protein is thought to interfere with key regulatory pathways such as WNT and apoptosis/cell cycle control pathways which may drive a leukemic process. The DNA-binding and protein dimerization domains of PBX1 replaces the TCF3 helix-loop-helix DNA-binding motif in ''TCF3-PBX1'' fusion. The remaining transcriptional activating domains of TCF3 leads to constitutive nuclear localization and transformation of PBX1 into an oncogenic transcriptional factor <ref>{{Cite journal|last=Diakos|first=Christofer|last2=Xiao|first2=Yuanyuan|last3=Zheng|first3=Shichun|last4=Kager|first4=Leo|last5=Dworzak|first5=Michael|last6=Wiemels|first6=Joseph L.|date=2014|title=Direct and indirect targets of the E2A-PBX1 leukemia-specific fusion protein|url=https://pubmed.ncbi.nlm.nih.gov/24503810|journal=PloS One|volume=9|issue=2|pages=e87602|doi=10.1371/journal.pone.0087602|issn=1932-6203|pmc=3913655|pmid=24503810}}</ref><ref name=":1" /><ref name=":0" />

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==Genetic Diagnostic Testing Methods==