ACY-1215 and IM synergistically inhibit CML cells in vitro and in vivo. (a, b) CML cells were exposed to ACY-1215 and IM for 48 h, apoptosis rate was detected by FCM. (c, d) In order to determine the cell viability, CCK-8 experiment was carried out. CompuSyn software was used to calculate the combination index (CI) values. CI < 1 means that the two drugs have a synergistic effect. (e) H&E was used to examine murine liver and spleen infiltration in four groups, and Wright's stain was used to examine bone marrow cells. Scale bar, 100 μm. (f) An immunofluorescence test was used to detect BCR/ABL expression. Scale bar, 50 μm. (g) Survival curves were analyzed by Kaplan–Meier methods using GraphPad Prism 8.0. *p < 0.05. (h) The working model of ACY-1215-induced cell apoptosis and cycle arrest in CML. ACY-1215 induced acetylation of Hsp90α, thus resulting in degradation of BCR-ABL. Besides, ACY-1215 increased the production of ROS and PTEN expression, which inhibited the PI3K/Akt pathway.