Project Funding Details

Billions of white blood cells are formed every day in the bone marrow. Leukemia occurs when cell proliferation becomes uncontrolled. As part of a complex ensemble of regulators of blood cells, the "Notch signaling pathway" helps maintain the balanced generation and proliferation of white blood cells. Several labs observed that increasing Notch signaling in Acute Myeloid Leukemia (AML) cells impairs their proliferation and may thus provide therapeutic benefit for AML patients. What mechanisms contribute to switching Notch signaling off in blood cells? Could these mechanisms be targeted for the therapeutic benefit of leukemia patients? The Rual lab recently discovered that the L3MBTL3 gene is a repressor of Notch signaling. We hypothesize that the inhibition of L3MBTL3 in AML cancer cells and the associated “de-repression” of Notch signaling could provide therapeutic benefit in AML. With the support of the B+ Foundation, we propose to test this hypothesis by studying the extent to which inhibiting L3MBTL3 modulates cancer progression in mouse models of AML. Our study could offer critical mechanistic insights on the role of the L3MBTL3 in AML that could be harnessed in the future for the therapeutic benefit of AML patients.