Novel Therapy May Overcome Chemotherapy Resistance in AML

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Researchers analyzed human AML samples to determine potential selective targets in leukemia stem cells, the source of resistance to standard chemotherapy.
Researchers analyzed human AML samples to determine potential selective targets in leukemia stem cells, the source of resistance to standard chemotherapy.

Dual inhibition of enhancer of zeste (EZH) 1 and 2 may prevent post-chemotherapy relapse among patients with acute myeloid leukemia (AML), according to an article published in Leukemia.1

Development and proliferation of AML is attributed to the formation of leukemia stem cells (LSCs), which, when quiescent, can also confer resistance to standard chemotherapy regimens. New strategies are therefore needed to help eliminate quiescent LSCs.

For this study, which included murine and patient-derived xenograft modeling, researchers analyzed AML samples to determine potential selective targets in LSCs. Chemotherapy was administered to mice to locate and analyze resistant AML cells.

The analyses showed that some LSCs are dependent on Ezh1 and Ezh2, and that quiescent cells showed high levels of EZH1/2. Inactivating EZH1/2 was shown to have curative potential in AML.

The authors noted that the EZH1/2 inhibitor improved survival in tested mice, and concluded that if this drug were combined effectively with standard chemotherapy, it “would represent the most effective treatment for AML treatment since the advent of all-trans-retinoic-acid for treating acute promyelocytic leukemia.”

Reference

  1. Fujita S, Honma D, Adachi N, et al. Dual inhibition of EZH1/2 breaks the quiescence of leukemia stem cells in acute myeloid leukemia. Leukemia. 2017 Sep 27. doi: 10.1038/leu.2017.300 [Epub ahead of print]

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