Inhibiting fundamental pathways for quiescence in acute myeloid leukemia: Hedgehog, Notch and WNT/Beta-Catenin

Current treatments for acute myeloid leukemia in young patients consist mainly of chemotherapy. The mode of action of these chemotherapeutics is directed at dividing cells; therefore, those cells that are outside the cell cycle are not eliminated. This is the case of leukemic stem cells, a population that is in quiescence and that can lead to relapse of patients in the disease. Possible ways to force cell cycle entry of this population, for example by inhibiting the conserved Hedgehog, Notch and WNT/Beta-Catenin pathways, are being studied. In this work we will study whether drugs against these pathways in combination with azacitidine can decrease cell viability versus treatment with the chemotherapeutic agent alone.