When compared to earlier chemotherapy treatments, these drugs have revolutionized CML treatment and allowed most people to live longer lives. Targeted medicines known as tyrosine-kinase inhibitors have dramatically improved long-term survival rates in CML patients during the previous 2 decades. Both genetic and epigenetic factors influence the efficacy of CML treatment strategies. There is strong evidence that disease progression, treatment responses, and overall clinical outcomes of CML patients are influenced by the accumulation of other genetic and epigenetic abnormalities, rather than only the BCR/ABL1 oncoprotein.

In other words, it is possible to develop the combination therapy of TKs with drugs targeting genes or molecules more specifically, which is required for survival mechanisms of CML LSCs, while sparing normal HSCs for clinical benefits along with TKIs.Ĭhronic myeloid leukemia is a malignancy of bone marrow that affects white blood cells. Targeting therapeutic approaches aim to eradicate CML LSCs through characterization and targeting genetic alteration and molecular pathways involving in CML LSC survival in a favorable leukemic microenvironment and resistance to apoptosis, with the hope of providing a functional cure. In fact, the maintenance CML LSCs in patients who are resistance to TKI therapy indicates the role of CML LSCs in resistance to therapy through survival mechanisms that are not completely dependent on BCR-ABL activity. Despite advances in the development of more potent tyrosine kinase inhibitors, some mechanisms particularly in terms of CML leukemic stem cell (CML LSC) lead to intrinsic or acquired therapy resistance, relapse, and disease progression. The combination with Dasatinib enhanced the HDAC inhibitory activity of Chidamide, promoted cell apoptosis and cell-cycle arrest of AML cells, and enhanced the inhibition of leukemia stem cell proliferation.Ĭhronic myeloid leukemia (CML) is a clonal myeloproliferative neoplasm driven by BCR-ABL1 oncoprotein, which plays a pivotal role in CML pathology, diagnosis, and treatment as confirmed by the success of tyrosine kinase inhibitor (TKI) therapy. Dasatinib and Chidamide had synergistic antitumor effect. The inhibitory rate of CD34+ CD38− HL-60 cells or Kasumi-1 cells was elevated when the cells were disposed with both Chidamide and Dasatinib. In the combined group, the proportion of S phase was significantly decreased, and the proportions of G2/M phase were significantly increased.

The combination of Dasatinib and Chidamide significantly enhanced the Abnormal histone deacetylase (HDAC) inhibitory activity of Chidamide in Kasumi-1 and HL-60 cells. The inhibition rate of the Dasatinib and Chidamide combination was significantly better than that of the single-drug application for HL-60 cells. This research aimed to explore whether Chidamide works synergistically with Dasatinib in the therapy of Acute myeloid leukemia (AML) and the potential molecular mechanism.

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