Bcl-2 or Bcl-xL overexpression is associated with relative GO resistance in HL-60-derivative cells, and PK11195 significantly increases GO cytotoxicity in these AML cells. Relative Bcl-2 and Bcl-xL overexpression in HL-60/Bcl-2 and HL-60/Bcl-xL cells was confirmed in Western blot analyses, in which we also found that NB4 and HL-60/AR cells relatively overexpress Bcl-2, TF1 cells relatively overexpress Bcl-xL, and ML-1 cells relatively overexpress proapoptotic Bax. The cytotoxicity of 0.2-40 ng/mL GO and 50-250 nM DOX was measured in HL-60/Bcl-2 and HL-60/Bcl-xL cells, and treated live cell fractions are displayed relative to untreated live cell fractions. While parental HL-60 cells were maximally killed by 10 ng/mL GO (Figure 3), statistically higher fractions of HL-60/Bcl-2 or HL-60/Bcl-xL cells survived at 10 and 40 ng/mL GO (^@P < .01, ^@@P < .001), compared to HL-60 cells treated with GO at the same doses (HL-60 data presented in Figure 3). PK11195 (50 μM) and CSA (2.5 μg/mL) were minimally cytotoxic in HL-60/Bcl-2 and HL-60/Bcl-xL cells and significantly (P < .01) increased cytotoxicity of GO at all doses tested in these cells. PK11195 significantly increased GO cytotoxicity (eg, P < .001 with 10 ng/mL GO) in HL-60/Bcl-xL cells to a greater degree than did CSA (eg, P < .01 with 10 ng/mL GO). CSA was ineffective in increasing DOX-induced cytotoxicity in HL-60/Bcl-2 and HL-60/Bcl-xL cells, whereas PK11195 significantly increased DOX-induced cytotoxicity in HL-60/Bcl-2 cells (P < .05) and tended to increase DOX-induced cytotoxicity in HL-60/Bcl-xL cells (P = .07). Data are shown as mean ± SEM from up to 3 independent experiments performed in duplicate or triplicate wells.