Grant: Operating Grant: Impact Grant : CEEHRC Phase II

T-cell Acute Lymphoblastic Leukemia (T-ALL) is an aggressive cancer of T-cell progenitors that occur in children and adults. While the prognosis of T-ALL patients has gradually improved with intensive chemotherapy treatment, these treatments are associated with acute and chronic toxicities that become apparent as children survive into adulthood. Furthermore, treatment options for patients with early relapse are very limited. Therefore, there is an urgent need to develop novel therapeutic approaches that are more effective and less toxic. Through a detailed molecular analysis of the oncogenic transcription factor TAL1 that is aberrantly expressed in 60% of T-ALL patients, we have recently demonstrated that the maintenance of a leukemia phenotype in TAL1-expressing T-ALL blasts is dependent on the activity of the epigenetic factor UTX that demethylates the repressive histone modification trimethylated H3K27. In this application, we propose an innovative method to develop a new therapeutic approach based on disrupting interactions between proteins involved in leukemia maintenance. We expect that these new approaches may led to the development of improved therapies for T-ALL.