The statin/UCN-01 regimen induces apoptosis in multiple leukemia and myeloma cell lines as well as primary AML cells but is minimally toxic to normal hematopoietic cells. (A) Human leukemia (Jurkat, HL-60, and Raji) and myeloma (RPMI8226 [8226], MM.1S, and MM.1R) cells were exposed to UCN-01 ([UCN] 100 nM for HL-60, RPMI8226, MM.1S, and MM.1R; 150 nM for Jurkat and Raji) with or without lovastatin ([LV] 20 μM for all leukemia cell lines; 10 μM for all myeloma cell lines) for 18 hours (leukemia cells) or 24 hours (myeloma cells), after which the percentage of annexin V⁺ cells was determined by flow cytometry. (B) AML blasts were isolated from peripheral blood samples derived from 3 patients with AML (FAB classification M2) as described in “Cells and reagents.” Mononuclear cells were isolated from the bone marrow (BM/MC) of 2 patients with nonmalignant, nonmyeloid hematopoietic disorders and the peripheral blood (PB/MC) from 1 healthy volunteer. AML blasts and normal cells were treated with 150 nM UCN-01 with or without 20 μM lovastatin for 18 hours, after which the percentage of apoptotic cells was determined by evaluating Giemsa-Wright–stained cytospin preparations. (C) U937 cells were incubated with UCN-01 (50 to 100 nM) with or without low doses of lovastatin (1 to 5 μM) for 48 hours or 72 hours, after which the percentage of annexin V⁺ cells, including annexin V⁺/PI⁻ and annexin V⁺/PI⁺, was determined by flow cytometry. (D) U937 and U266 cells were treated with UCN-01 (U937, 100 nM; U266, 150 nM) with or without lovastatin (U937, 20 μM; U266, 10 μM) for 18 hours (U937) or 48 hours (U266), after which cells were washed free of drug and plated in soft agar as described in “Analysis of apoptosis and clonogenicity.” After incubation for 12 days, colonies (more than 50 cells) were scored, and colony formation for each condition expressed relative to untreated control cells. For all panels, results represent the means ± SD for 3 separate experiments performed in triplicate.