Deacetylation of YAP1 Promotes the Resistance to Chemo- and Targeted Therapy in FLT3-ITD⁺ AML Cells.

ABSTRACT: The FLT3-ITD mutation occurs in about 30% of acute myeloid leukemia (AML) and is associated with poor prognosis. However, FLT3 inhibitors are only partially effective and prone to acquired resistance. Here, we identified Yes-associated protein 1 (YAP1) as a tumor suppressor in FLT3-ITD⁺ AML. YAP1 inactivation conferred FLT3-ITD⁺ AML cell resistance to chemo- and targeted therapy. Mass spectrometric assay revealed that DNA damage repair gene poly (ADP-ribose) polymerase 1 (PARP1) might be the downstream of YAP1, and the pro-proliferative effect by YAP1 knockdown was partly reversed via PARP1 inhibitor. Importantly, histone deacetylase 10 (HDAC10) contributed to decreased YAP1 acetylation levels through histone H3 lysine 27 (H3K27) acetylation, leading to the red

SUBMITTER: Feng P 

PROVIDER: S-EPMC9152322 | biostudies-literature | 2022

REPOSITORIES: biostudies-literature