PEP005 induces apoptosis in primary AML marrow blasts but not in normal myeloblasts. (A) PEP005 induced apoptosis in a primary AML cell culture. Apoptosis was determined by appearance of a subdiploid peak (▪) or active caspase-3 (•). (B) Meaned data for apoptosis induction by PEP005 in 7 primary AML samples. Data are mean ± SD. ^*P < .01 compared with non-parallel-treated controls. (C) Morphology on cytospins of example AML and nonmalignant CD34⁺ myeloblasts from cord blood after treatment with 20 nM PEP005 and 200 nM PEP005, respectively. Differential staining showed that normal myeloblasts did not enter apoptosis, but when exposed to higher concentrations of PEP005 had a more differentiated phenotype. (D) An example of a FACS plot of nonmalignant myeloblasts treated with PEP005, showing reduced CD34 staining indicative of differentiation.