MCL-1 expression dictates response mediated by inhibition of BCR-ABL. (A-B) In vitro–generated BCR-ABL (p185)–expressing Arf^−/− cells were treated with IM or DAS in the presence or absence or IL-7 (20 ng/mL) at varying concentrations (24 hours) (A) or with the indicated IM or DAS concentrations for different amounts of time (hours) (B). Cell lysates were resolved and immunoblotted for indicated targets. Anti-ABL antibody was used to detect the BCR-ABL fusion protein, and pBCR-ABL and pSTAT5 represent phosphorylated proteins. (C) Immunoblot of p185-expressing cells that were derived from wild-type Mcl-1 (Mcl-1^wt), haploinsufficient (Mcl-1^het, 1 floxed Mcl-1 allele deleted using p185-IRES-Cre retrovirus), or overexpressing ectopic Mcl-1 in addition to endogenous (Mcl-1^OE) on an Arf^−/− genetic background. Cell lysates were resolved and immunoblotted for MCL-1 and actin (loading control). (D-E) Cells described in (C) or p185-expressing Arf^−/− pre–B cells were treated for 24 hours at indicated doses with IM (D) or DAS (E) after which cell death was determined. Cells were cultured in the presence of IL-7 (20 ng/mL) where indicated. Annexin-V and PI double-negative cells were scored as viable. Data points represent the average of 3 independent experiments (n = 3), and the error bars denote the standard error of the mean (SEM).