Screening for drivers and dependency factors in a novel genetic model for T-ALL in Xenopus tropicalis

01 October 2018 → 31 December 2022
Research Foundation - Flanders (FWO)
Research disciplines
  • Medical and health sciences
    • Cancer biology
Project description

Acute lymphoblastic leukemia (ALL) is an aggressive tumor entity of highly proliferative malignant
lymphoid cells. This leukemia subtype is one of the most common childhood malignancies
worldwide. T-ALL is a particularly aggressive hematologic cancer resulting from the malignant
transformation of T-cell progenitors. Despite our good and improving understanding of the
genomic defects in human T-ALL, leukemia patients are still treated by high dose multi-agent
chemotherapy, potentially followed by hematopoietic stem cell transplantation, and patients may
still relapse and present with very unfavorable survival perspectives. Therefore, better patient
stratification and patient-tailored targeted therapies are required to improve treatment of T-ALL.
Due to whole genome sequencing projects on patient samples, we get a better understanding of
the disease. In this project we want to exploit a novel genetic model in the frog Xenopus
tropicalis. We use CRISPR/Cas9, a technique allowing fast, cheap and efficient gene disruption, for
the characterization of novel candidate driver mutations and for identification of so called
“dependency genes”, which encode proteins on which the cancer cells rely for their proliferative
and malignant behavior. Identification of these dependency factors will open the road for novel
targeted drug development efforts that could be beneficial for a wider range of hematologic
malignancies as well as solid tumors.