Prognostic significance of protein-coding and long non-coding RNA expression profile in T-cell acute lymphoblastic leukemia

T-acute lymphoblastic leukemia (T-ALL) is an aggressive hematological malignancy associated with poor outcome. To unravel gene-expression profile of immunophenotypic subtypes of T-ALL, we did transcriptome analysis in 35 cases. We also analyzed the prognostic relevance of 23 targets: protein-coding genes, histone modifiers and long non-coding RNA (lncRNA) expression profile, identified on RNA sequencing, on an independent cohort of 99 T-ALL cases. We found high expression of MEF2C to be associated with prednisolone resistance ( p= 0.048) and CD34 expression ( p =0.012). BAALC expression was associated with expression of CD34 ( p= 0.032) and myeloid markers ( p= 0.021). XIST and KDM6a expression levels were higher in females ( p= 0.047 and 0.011, respectively). Post-induction minimal residual disease (MRD) positivity was associated with high lncRNA PCAT18 ( p= 0.04), HHEX ( p= 0.027) and MEF2C ( p= 0.007). Early thymic precursor (ETP-ALL) immunophenotype was associated with high expression of MEF2C ( p= 0.003), BAALC ( p= 0.003), LYL1 ( p= 0.01), LYN ( p= 0.01), XIST ( p= 0.02) and low levels of ST20 ( p= 0.007) and EML4 (p=0.03). On survival analysis, MEF2C high expression emerged as significant predictor of 3-year event free survival (EFS) (low 71.78±6.58% vs high 36.57±10.74%, HR 3.5, p= 0.0003) and overall survival (OS) (low 94.77±2.96% vs high 78.75±8.45%, HR 4.88, p= 0.016) in our patients. LncRNA MALAT1 low expression also emerged as predictor inferior OS (low 76.02±10.48 vs high 94.11±3.31, HR 0.22, p= 0.027).