Chidamide in FLT3-ITD positive acute myeloid leukemia and the synergistic effect in combination with cytarabine.

Abstract

Chidamide, a novel histone deacetylase inhibitor (HDACi), has been approved for treatment of T-cell lymphomas in multiple clinical trials. It has been demonstrated that chidamide can inhibit cell cycle, promote apoptosis and induce differentiation in leukemia cells, whereas its effect on acute myeloid leukemia (AML) patients with FLT3-ITD mutation has not been clarified. In this study, we found that chidamide specifically induced G0/G1 arrest and apoptosis in FLT3-ITD positive AML cells in a concentration and time-dependent manner. We also found chidamide had the cytotoxicity effect on FLT3-ITD positive and negative AML cells. Moreover, with respect to relapsed/refractory patients, chidamide showed the same effectiveness as that in de novo AML patients. Notably, chidamide synergistically enhanced apoptosis caused by cytarabine. Our results support chidamide alone or combine with cytarabine may be used as an alternative therapeutic choice for AML patients especially those with FLT3-ITD mutation or relapsed/refractory ones.