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

{{DISPLAYTITLE:B lymphoblastic leukaemia/lymphoma with TCF3::PBX1 fusion}}

{{Under Construction}}

}}</blockquote>

==Primary Author(s)*==

==Clinical Features==

{| class="wikitable"

|'''Signs and Symptoms'''

|-

|'''Laboratory Findings'''

|}

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

==Immunophenotype==

{| class="wikitable sortable"

!Finding!!Marker

|-

|-

|-

|-

|}

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

!Notes

|-

|Yes

|No

|Yes

The t(9;22) is diagnostic of CML in the appropriate morphology and clinical context (add reference). This fusion is responsive to targeted therapy such as Imatinib (Gleevec) (add reference).

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

* Chromosomal Rearrangements (Gene Fusions)

* Individual Region Genomic Gain/Loss/LOH

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

{| class="wikitable sortable"

!Notes

|-

7

chr7:1- 159,335,973 [hg38]

chr7

|Yes

|No

Presence of monosomy 7 (or 7q deletion) is sufficient for a diagnosis of AML with MDS-related changes when there is ≥20% blasts and no prior therapy (add reference).  Monosomy 7/7q deletion is associated with a poor prognosis in AML (add reference).

|-

8

chr8:1-145,138,636 [hg38]

chr8

|No

|No

Common recurrent secondary finding for t(8;21) (add reference).

|}

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

==Characteristic Chromosomal Patterns==

{| class="wikitable sortable"

!Notes

|-

Co-deletion of 1p and 18q

|No

|No

See chromosomal rearrangements table as this pattern is due to an unbalanced derivative translocation associated with oligodendroglioma (add reference).

|}

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>  

==Gene Mutations (SNV / INDEL)==

{| class="wikitable sortable"

!Notes

|-

EGFR; Exon 20 mutations

|

|

|

<br />

|}

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

==Genes and Main Pathways Involved==

{| class="wikitable sortable"

|-

!Gene; Genetic Alteration!!Pathway!!Pathophysiologic Outcome

|-

|-

|-

|}

''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" />