BIRC5 Upregulation Enhances DNMT3A-Mutant T-ALL Cell Survival and Pathogenesis

The goal of this study was to determine how patients with T-ALL who have DNA methyltransferase 3 alpha (DNMT3A) mutations develop resistance to therapy. Since DNMT3A is a methyltransferase, we examined the effect of those mutations on epigenetic regulation using whole genome bisulfite sequencing (WGBS). We also assessed any changes in gene expression using RNA-sequencing. We found that T-ALL patients with DNMT3A mutations are resistant to apoptosis and some chemotherapies. WGBS showed that DNMT3A mutated patients clustered together by their epigenetic profile, which was associated with hypomethylation at TERT and HOX genes. RNA sequencing identified differences in JAK/STAT signaling. ]]>
Inclusion criteria: Patients with T-ALL, who had cryopreserved specimens and were consented to the research study. Exclusion criteria: Absence of T-ALL. ]]>
T-ALL is an aggressive blood cancer. In adults T-ALL is difficult to treat and associated with poor outcomes. Understanding the mechanisms of T-ALL development and treatment resistance is important for developing novel therapies for this disease. ]]>