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.