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

01 January 2022 → Ongoing
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.