Central role of caspase-9 in MDS bone marrow cell apoptosis.

(A) Spontaneous caspase-9 activity was determined in MNCs derived from RA, RARS, and NBM at 18 hours of in vitro culture. Caspase-9 activity was significantly elevated in RARS (P < .05). Elevated levels of caspase-9 activity were also apparent in RARS cells at 8 hours of incubation (data not shown). The difference between RA and NBM was not statistically significant (P = .17). (B) Cells from 22 patients and 10 controls were incubated for 4 hours in the presence or absence of the selective caspase-9 inhibitor, LEHD-fmk (20 μM). Caspase-9 inhibition significantly decreased caspase-3–like activity in both RA and RARS (P < .0001). A similar inhibition of caspase-3–like activity was observed in NBM cultures (P < .05).