FIGURE 6.

Chidamide-potentiated YAP1 expression and the combination chidamide with FLT3 inhibitors or chemotherapy agents synergistically promoted apoptosis in the acquired resistant FLT3-ITD⁺ AML cells ex vivo. (A) Expression level of YAP1 was analyzed by Western blot in FLT3-ITD⁺ AML cells after treatment with chidamide for 24 h. (B) and (C) Apoptosis rate was analyzed by flow cytometry in relapse FLT3-ITD⁺ AML patient cells after treatment with chidamide (2 or 4μM) combined with sorafenib (50 or 100 nM). (D) and (E) Apoptosis rate was analyzed by flow cytometry in relapse FLT3-ITD⁺ AML patient cells after treatment with chidamide (2 or 4nM) combined with HHT (1 or 2 nM) or Ara-C (0.2 or 0.4μM). (F) Schematic summary of this study. HDAC10 mediates the chemoresistance of FLT3-ITD⁺ AML cells to FLT3 inhibitors by deacetylating YAP1. Targeting the HDAC10 sensitizes FLT3-ITD⁺ AML cells to FLT3 inhibitor treatment by enhancing acetylation of YAP1 through acetyl H3K27, promoting its transcriptional control, and strengthening nuclear YAP1-induced DNA damage repair. Data are shown as mean ± SD of three independent experiments; *p < 0.05; **p < 0.01.