IRIC, University of Montréal
A developmental checkpoint in Pro-T cells and acute leukemia
Acute lymphoblastic leukemia is the most common childhood cancer and 25% of those are of T cell origin (T-ALL). Approximately 20% of childhood and 60% of adolescent and adult patients succumb to this disease. Furthermore, even though the disease is of good prognosis in children and treatment can achieve more than 80% long term cure, current chemotherapy compounds impose a severe burden on the patient and the immediate family, due to undesirable severe side effects. There is an urgent need to identify compounds that are more specific towards leukemic cells and spare normal cells. To this end, we used a multilevel approach to identify the complete set of molecular alterations that lead to T-ALL, with the ultimate goal of identifying more specific drug-like compounds that can efficiently inhibit T-ALL maintenance and propagation. We uncovered a novel mechanism that controls disease onset, due to alterations of a critical quality control checkpoint in T-cell development. We propose a global approach combining large scale genomic, bioinformatics and cell based screening with in vivo models of T-ALL to identify more specific drugs. Our research opens possibilities for new treatments of T-ALL.