Effect of SFK inhibition using dasatinib on apoptosis and growth of primitive and committed progenitors. (A) CFC assay of AML (n = 9; left; ***P < .001) or normal CD34+ cells (n = 11; 6 PBSC and 5 CB; ns, nonsignificant; *P < .05; ***P < .001) exposed to increasing doses of dasatinib for 48 hours. Results shown are presented as percentage of control (mean ± SEM). (B) LTC-IC assays of AML (left; n = 5; **P < .01) or normal CD34+ (right; n = 4; 2 CB and 2 PBSC; ns, nonsignificant) cells treated with dasatinib. The percentage inhibition of LTC-IC frequency relative to untreated controls is shown for AML. (C) Apoptosis of AML (n = 4) and normal CD34+ (n = 6; 3 PBSC, 3 CB) cells cultured for 48 hours with indicated concentrations of dasatinib. Results shown are presented as mean ± SEM of Annexin V-positive cells in treated vs untreated cells. ns, non significant; *P < .05; **P < .01; ***P < .001. (D) PI of AML CD34+ cells determined by CFSE labeling assays. The PI was determined using ModFit software and proliferation indices were normalized to untreated controls. Compiled data for proliferation of 5 AML is shown (*P < .05). (E) Cell cycle analysis of AML progenitors CD34+ (n = 7), using Ki-67 and 7-AAD staining (ns, nonsignificant; **P < .01).