Expression of Bcl-2 family proteins in HMCLs. (A) Immunoblot analysis of the antiapoptotic proteins Mcl-1, Bcl-2, and Bcl_xL. The most GX015-070–sensitive HMCLs, JJN3, KMS18, SKMM2, H929, MY5, KMS12PE, and MY7 (IC₅₀ ≤ 150 nM), lack or nearly lack Bcl_xL. On the other hand, more resistant cell lines (IC₅₀ ≥ 300 nM) express abundant levels of all 3 antiapoptotic proteins. (B) Immunoblot analysis of proapoptotic proteins Bim-EL, Bim-L, Bim-S, Bax, and Bak. A correlation between decreased Bak expression (KMS18, SKMM2, MY5, KMS12PE, and MY7) and response to GX015-070 was observed. Protein expression determined by densitometric measurement is listed in Table 2. (C) Mcl-1 expression in primary MM and MGUS samples. The median normalized gene expression of Mcl-1 is shown for HMCL and for CD138⁺ marrow populations from MM, SMM, or MGUS patients and is compared with normal BM plasma cells. Each data point represents the mean of all 5 Mcl-1 probe sets present on the Affymetrix U133A chip (Palo Alto, CA). There is consistently higher median expression of Mcl-1 in MM than in HMCL.