Fig. 5.

Small-molecule inhibition of IRE1α kinase reduces viability of CD138⁺ MM cells in patient-derived samples without disrupting CD138⁻ cells. (A–E) Bone marrow aspirates or peripheral blood obtained in the United States (A, C, and E) or European Union (B and D) from patients with newly diagnosed (NDx) or relapsed MM. Further information about age, gender, disease state, cytogenetics, and prior treatments is included in SI Appendix, Fig. S5A. Samples were cultured for 48 (A–C and E) or 72 h (D) with either vehicle (DMSO) or 10 μΜ compound (Cpd) 18 (A, B, and E), or two dose levels, 1 and 10 μΜ of compound (Cpd) 18 (C and D). Samples were then analyzed for viability by flow cytometry, with gating on CD138⁺ or CD138⁻ cells. Nonmalignant bone marrow aspirates (n = 3) were similarly tested and are depicted for comparison (E). Data represent mean ± SD of triplicate determinations except where triplicates were not possible due to insufficient sample size. NS, not significant. *P < 0.05, ***P ≤ 0.001.