Dual targeting of CDK6 and LSD1 is synergistic and overcomes differentiation blockade in AML.

ABSTRACT: The heterogeneity of leukemic cells is the main cause of resistance to therapy in acute myeloid leukemia (AML). Consequently, innovative therapeutic approaches are critical to target a wide spectrum of leukemic clones, regardless of their genetic and non-genetic complexity. In this report, we leverage the vulnerability of AML cells to CDK6 to identify a combination therapy capable of targeting common biological processes shared by all leukemic cells, while sparing non-transformed cells. We demonstrate that the combined inhibition of CDK6 and LSD1 restores myeloid differentiation and depletes the leukemic progenitor compartment in AML samples. Mechanistically, this combination induces major changes in chromatin accessibility, leading to the transcription of differentiation genes and diminis

SUBMITTER: Brault L 

PROVIDER: S-EPMC12514269 | biostudies-literature | 2025 Oct

REPOSITORIES: biostudies-literature