Arginine dependence of acute myeloid leukemia blast proliferation: a novel therapeutic target

摘要: Acute myeloid leukemia (AML) is one of the most common acute leukemias in adults and children, yet significant numbers patients relapse die disease. In this study, we identify dependence AML blasts on arginine for proliferation. We show that constitutively express transporters CAT-1 CAT-2B, majority newly diagnosed patients’ have deficiencies arginine-recycling pathway enzymes argininosuccinate synthase ornithine transcarbamylase, making them auxotrophic. BCT-100, a pegylated human recombinant arginase, leads to rapid depletion extracellular intracellular concentrations, resulting arrest blast proliferation reduction engraftment vivo. BCT-100 as single agent causes death from acts synergistically combination with cytarabine. Using RNA sequencing, 20 further candidate genes which correlated resistance been identified. Thus, are dependent survival proliferation, well clinical value treatment AML.