In this preclinical study, we found a regimen combining Bcl-2 inhibitor ABT-199 with low dose of the HDACi (CS055), both of which have been approved for the treatment of certain hematologic malignancies, displayed the superb anti-leukemic activity against AML cells and CD34+/CD38− leukemic stem/progenitor cells, whereas largely sparing normal hematopoietic progenitors. The gene discussed is CD38; the disease is acute myeloid leukemia.