Copy Number Alterations in CDKN2A/2B and MTAP Genes Are Associated With Low MEF2C Expression in T-cell Acute Lymphoblastic Leukemia

The molecular heterogeneity of T-cell acute lymphoblastic leukemia (T-ALL) makes this disease complex. Early T-cell precursor ALL (ETP-ALL) is a recognized subtype of T-ALL associated with a high probability of induction failure with conventional therapy. Higher expression of myocyte enhancer factor...

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Published in:Curēus (Palo Alto, CA) CA), 2022-12, Vol.14 (12), p.e32151-e32151
Main Authors: Kumari, Sarita, Singh, Jay, Arora, Mohit, Ali, M Shadab, Pandey, Avanish K, Benjamin, Mercilena, Palanichamy, Jayanth Kumar, Bakhshi, Sameer, Qamar, Imteyaz, Chopra, Anita
Format: Article
Language:English
Subjects:
Cell cycle
Cyclin-dependent kinases
Gene expression
Hematology
Kinases
Leukemia
Medical prognosis
Oncology
Patients
Pediatrics
T cell receptors
Therapeutics
Transcription factors
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Summary:The molecular heterogeneity of T-cell acute lymphoblastic leukemia (T-ALL) makes this disease complex. Early T-cell precursor ALL (ETP-ALL) is a recognized subtype of T-ALL associated with a high probability of induction failure with conventional therapy. Higher expression of myocyte enhancer factor 2C ( ) and the absence of a biallelic deletion (ABD) are the designated markers for the ETP-ALL. Co-deletion of the contiguous genes cyclin-dependent kinase inhibitor 2A/2B ( / and the methylthioadenosine phosphorylase ( cluster, located at 9p21.3, is another common alteration in T-ALL and confers poor response to treatment. We used real-time polymerase chain reaction (PCR) analysis to assess mRNA expression and ABD status. Copy number alterations (CNAs) in key genes previously reported to be altered in T-ALL were assessed using multiple ligation probe amplification (MLPA). We observed that CNAs in this co-deletion cluster of and genes exhibited low expression while ABD was associated with CNA in the Abelson murine leukemia 1 ( gene. Assessment of expression based on immunophenotype revealed that its association with alteration is present in non-immature immunophenotype. Additionally, ABD was associated with copy number alterations of T-cell acute lymphocytic leukemia protein 1 ( , myeloblastosis ( , and LIM domain only 2 ( genes in immature immunophenotypes. Further,  fusion was associated with low expression of  . These associations may help explain the difficulties in assessing disease heterogeneity and the prognostic importance of 9p21.3 alterations in T-ALL.
ISSN:2168-8184
2168-8184
DOI:10.7759/cureus.32151