According to prior research, the PI3K/Akt signal pathway is dysregulated in response to the activation of BCR–ABL, which is also modulated in response to IM treatment.38 Additionally, the inhibition of PI3K/Akt sensitizes the CML leukemic stem cells to TKIs.39 Liu et al. suggested that PI3K/Akt blocking within the bone marrow stromal cells dramatically reduced the IM resistance induced by HO-1.40 As shown in our study, the Akt signaling pathway had a negative effect on regulating apoptosis, so the HDAC2 effect on Akt activity in CML cells resistant to IM was also investigated. This evidence concerns the gene BCR and chronic myelogenous leukemia, BCR-ABL1 positive.