Prevalence of Mutations in TAL1 Gene in Individuals With T-ALL and T-NHL

Abstract

Mutations in the TAL1 (T-cell acute leukemia 1) gene were recently described in patients with T-cell acute lymphoblastic leukaemia (T-ALL) and in those with lymphoblastic T-cell non-Hodgkin‘s lymphoma (T-NHL). The purpose of this pilot study was to assess the prevalence of mutations in TAL1 gene in T-ALL and TNHL. DNA samples from 15 unrelated healthy controls, 20 T-ALL patients, and 10 T-NHL patients were analyzed using DNA-PCR and direct DNA sequencing to identify sequence genetic variations in TAL1 gene (exons 2 and 3). TAL1 exon 2 mutations were identified in 7.7% adult and 12.5% adolescent T-ALL patients analyzed. TAL1 exon 2 mutations were detected in 16.7% of the adult TNHL patients analyzed. Sequencing of TAL1 exon 3 showed no sequence variation for the T-ALL and T-NHL cancer patients analyzed. No sex difference where observed in the incidences of TAL1 exons 2 mutations between T-ALL and T-NHL patients with and without TAL1 mutations. TAL1 exon 2 missense and frame-shift mutations were present in 44.4% (4/9) and 55.6% (5/9) of T-ALL patients, respectively. However, the frame-shift and missense mutations in the T-NHL patients accounted for, where respectively, 60% (3/5) and 40% (4/5) of all TAL1 exon 2 mutations. Comparing the clinical features showed that there are no differences in PLT and WBC counts as well as the average age between T-ALL and T-NHL patients with and without TAL1 mutations. Overall, these findings indicate that TAL1 mutations are too rare to be of clinical relevance, and do not seem to be significantly associated with the increased T-ALL and T-NHL susceptibility, implying different pathways with respect to TAL1 genetic polymorphisms as a risk factor for T-ALL and T-NHL at least in this population of Libyans.