USE OF MYELOPEROXIDASE (MPO) INHIBITORS FOR THE TREATMENT OF CHEMORESISTANT ACUTE MYELOID LEUKEMIA (AML)

摘要

Chemotherapy commonly alters cellular redox balance and increases the oxidative state. Recent studies have reported that chemoresistant cells have an increased reactive oxygen species (ROS) content in hematological malignancies. Here the inventors demonstrate that chemoresistant acute myeloid leukemia (AML) cells have a decreased level of mitochondrial and cytosolic ROS associated with an overexpression of myeloperoxidase (MPO), a heme protein that converts chloride and hydrogen peroxide to hypochlorous acid (HOC1). They also show that high MPO-expressing AML cells are less sensitive to AraC in vitro and in vivo. Targeting MPO expression and enzyme activity sensitizes to AraC treatment by triggering sustained oxidative stress in the high MPO expressing AML cells. Thus the present invention relates to use of myeloperoxidase (MPO) inhibitors for the treatment of chemoresistant acute myeloid leukemia (AML).