Functional analysis of the RNA helicase DHX15 in T-cell acutelymphoblastic leukemia

01 January 2022 → 31 December 2024
Research Foundation - Flanders (FWO)
Research disciplines
  • Natural sciences
    • Analysis of next-generation sequence data
  • Medical and health sciences
    • Cancer biology
RNA splicing Leukemia Oncogene stability DHX15
Project description

T-ALL is an aggressive hematologic malignancy that requires treatment with intensified chemotherapy. Studies of the long-term effects of chemotherapy in patients with T-ALL showed that recent gains in leukaemia-free survival have been achieved at the cost of significant increased rates of life-threatening and debilitating toxicities. Thus, a better understanding of disease biology will be required to develop novel molecular targeted antileukemic drugs. RNA helicases are highly conserved enzymes that are implicated in pre-mRNA splicing, RNA export, RNA decay, ribosome biogenesis, transcription and translation. However, their role in T-ALL disease biology remains largely unexplored. Here, we identified DHX15 as an RNA helicase that is overexpressed in T-ALL and interacts with both NOTCH1 and MYC, two critical oncogenes that have been implicated in the development of this hematological disease. In this research proposal, we aim to identify the role of the RNA helicase DHX15 in the biology of T-ALL. More specifically, we want to investigate the functional relevance of its interaction with NOTCH1 and MYC and elucidate the downstream molecular mechanisms that might mediate its potential role as an oncogenic dependency factor in this haematological disease.