Activating leukemia stem cells makes chemotherapy more effective in AML

MD Anderson Research Highlight May 02, 2025

Acute myeloid leukemia (AML) is a hard-to-treat cancer in which certain leukemia stem/progenitor cells (LSPCs) hide in the bone marrow and resist treatment. Researchers led by Michael Andreeff, M.D., Ph.D., and Yuki Nishida, M.D., Ph.D., examined valemetostat, which targets EZH1 and EZH2 – proteins linked to keeping these LSPCs dormant. While valemetostat alone does not directly fight leukemia, it can wake up hidden LSPCs, making them vulnerable to chemotherapy. In lab models, researchers demonstrated that valemetostat improved the activity of cytarabine, a standard AML treatment, to kill more LSPCs and extend survival. Valemetostat did not harm normal stem cells, which shows that it specifically targets cancer. The drug did not improve responses with another therapy, venetoclax/azacitidine. Researchers discovered the same mobilizing effect on LSPCs in a clinical trial of valemetostat led by Naval Daver, M.D. These findings suggest that EZH1/2 inhibition could be a promising approach for improving AML treatment. Learn more in Blood Cancer Journal.