Figure 1

Myeloma cells were heterogeneously sensitive to RITA. A,D. LD₅₀ values for RITA (A) and nutlin3a (D) of HMCLs were plotted against the TP53 status of HMCLs. wt: wild type, m: mutated, trunc: truncated, KO: deleted. Cells (100,000/0.2 ml) from 32 HMCLs were incubated for 72 h with serial dilutions of RITA (20 μM to 1 nM) or nutlin3a (20 μM to 1.25 μM), and cell death was assessed using flow cytometry after APO2.7 staining (Cell Quest software, FACSCalibur). The LD₅₀ was defined as the concentration that killed 50% of cells (mean of 3 experiments). wt: wild-type, m:mutated, trun: truncated, KO: deleted. B,E. Contingency analysis of the sensitivity of HMCLs to RITA (B) or nutlin3a (E) with respect to TP53 status. C,F. The LD₅₀ values for RITA (C) and nutlin3a (F) of HMCLs were plotted against the 14q32 status of the HMCLs. Circle and triangle symbols represent TP53 ^wt and TP53 ^Abnormal HMCLs, respectively. G. Apoptosis induced by RITA and nutlin3a in normal PBMCs. PBMCs were incubated for 3 days in RPMI1640 medium containing 5% FCS with serial concentrations of RITA or nutlin3a. Data represent the mean ± SE of 3 independent donors.