Abstract 5233: MEF2C dysregulation is associated with immature T cell immunophenotype, absence of biallelic deletion of TCR-gamma and inferior survival

Abstract

Abstract T-cell acute lymphoblastic leukemia (T-ALL) is an aggressive hematological malignancy affecting both children & adults. Unlike B-ALL, the prognostic markers are not clearly defined in T-ALL. In this study, we evaluated the correlation of MEF2C gene expression in T-ALL with immunophenotype & absence of biallelic deletion of TCR-gamma (ABD) & tested its potential significance as prognostic marker. A total of 106 T-ALL patients, including 75 children & 31 adults (males 93; females 13) were included. Immunophenotyping was done in all cases at diagnosis on bone marrow/peripheral blood samples using CD3, CD7, CD4, CD2, CD45, CD5, CD8, CD1a, CD13, CD33, CD117, HLA-DR, CD34, CD65 & CD11b antibodies. The patients were categorized into immature (pre & pro T-ALL; n=48), cortical (n=47) & mature (n=11) T-ALL based on immunophenotypic features. MEF2C gene expression was quantified by RQ-PCR. ABD was done in 90 patients in which DNA was available by quantitative DNA PCR (Q-PCR) for TCR-gamma rearrangements using the protocol described before1. Minimal residual disease in bone marrow samples at the end of induction therapy was also measured. Kruskal-Wallis test was performed to determine the correlation of MEF2C expression with immunophenotypes & TCR-gamma chain status. Kaplan Meier survival analysis was done to evaluate the significance of MEF2C dysregulation on event free survival & overall survival. We found MEF2C gene to be significantly overexpressed (p=0.013) in patients with immature T-ALL as compared to cortical & mature T-ALL cases. It was significantly overexpressed in early T-cell precursor (ETP-ALL) cases (n=15) versus non ETP-ALL (p=0.03). By qPCR, 29 of 90 patients (32.22%) were classified as ABD, 44 (48.89%) as non-ABD & 17 (18.89%) as indeterminate. MEF2C expression was higher in ABD patients (p=0.011). Minimal residual disease was found more frequently in MEF2C dysregulated patients (p=0.033). On Kaplan Meier survival analysis, event free survival (EFS) was not significantly different between two groups (p=0.33). Overall survival (OS) was worse in MEF2C dysregulated patients as compared to others (p=0.017). ETP-immunophenotype was associated with poorer EFS (p=0.013). ABD did not correlate with EFS & OS. To conclude, MEF2C dysregulation was associated with immature T-immunophenotype, ABD & inferior survival at diagnosis. MEF2C gene expression can be used as potential candidate to risk stratify T-ALL cases. Reference 1. Gutierrez A, Dahlberg SE et al. Absence of biallelic TCRgamma deletion predicts early treatment failure in pediatric T-cell acute lymphoblastic leukemia. J Clin Oncol. 2010;28:3816-23. Citation Format: Anita Chopra, Jay Singh, Deepak Verma, Rajive Kumar, Sameer Bakhshi, Jayanth Kumar, Rachna Seth, Atul Sharma. MEF2C dysregulation is associated with immature T cell immunophenotype, absence of biallelic deletion of TCR-gamma and inferior survival [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 5233.