Risk stratification of T-cell Acute Lymphoblastic Leukemia patients based on gene expression, mutations and copy number variation. (June 2016)

• Record Type: Journal Article
• Authors: Mirji, Gauri; Bhat, Jaydeep; Kode, Jyoti; Banavali, Shripad; Sengar, Manju; Khadke, Prashant; Sait, Osama; Chiplunkar, Shubhada
• Is Part Of: Leukemia research. Volume 45(2016:Jun.)
• Page Start: 33
• Page End: 39
• Publication Date: 2016-06
• Subjects: T-ALL T-cell acute lymphoblastic leukemia -- CNV copy number variation -- ddPCR droplet digital PCR -- OS overall survival -- DFS disease free survival; Gene expression profiling -- T-ALL -- Droplet digital PCR -- Copy number variation -- Mutations -- TCRγδ + T-ALL; Leukemia -- Periodicals; Leukemia -- Periodicals; Leucémie -- Périodiques; Leukemia; Periodicals; Electronic journals; Electronic journals; 616.9941905
• DOI: 10.1016/j.leukres.2016.03.002
• Languages: English
• ISSNs: 0145-2126

Abstract

Highlights: TCRγδ + T-ALL is a distinct subgroup based on gene expression, CNV and mutations. Patients with homozygous deletion of CDKN2A/CDKN2B show inferior DFS. TCR clonality along with CDKN2A/CDKN2B CNV can act as prognostic marker in T-ALL. Abstract: Gene expression, copy number variations (CNV), mutations and survival were studied to delineate TCRγδ + T-cell acute lymphoblastic leukemia (T-ALL) as a distinct subgroup from TCRαβ + T-ALL. Gene Ontology analysis showed that differential regulation of genes involved in pathways for leukemogenesis, apoptosis, cytokine-cytokine receptor interaction and antigen processing/presentation may offer a survival benefit to TCRγδ + T-ALL patients. Genes involved in disease biology and having equal expression in both the subgroups, were further analysed for mutations and CNV using droplet digital PCR. TCRγδ + T-ALL patients exhibited differential level of mutations for NOTCH1 and IKZF3 ; however BRAF mutations were detected at equal levels in both the subgroups. Although TCRγδ + T-ALL patients with these mutations demonstrated improved disease-free survival (DFS) as compared TCRαβ + T-ALL patients, it was not statistically significant. Patients with homozygous deletion of CDKN2A/CDKN2B showed poor DFS in each subgroup. TCRγδ + T-ALL patients with wild type/heterozygous deletion of CDKN2A/CDKN2B possess significantly better DFS over TCRαβ + T-ALL patients (p = 0.017 and 0.045, respectively). Thus, the present study has for the first time demonstrated TCRγδ clonality and CDKN2A/CDKN2B CNV together as potential prognostic markers in management of T-ALL. Further understanding the functional significance of differentially regulated genes in T-ALL patients would aid in designing risk based treatment strategies in subset specific manner.