Effect of BMSCs on antitumor activity of nutlin-3a in primary myeloma isolates. (A) Survival of primary MM cells after 5-day incubation with either 10 μM nutlin-3a (•) or 10 μM nutlin-3b (▾) in medium supplemented with 10 ng/ml IL-6 (▿, ○) or in coculture with BMSCs (▾, •). The median values of survival relative to the DMSO control (indicated by bars) were 23% (nutlin-3a) and 87% (nutlin-3b) in medium supplemented with IL-6 and 43% (nutlin-3a) and 95% (nutlin-3b) for coculture with BMSCs (^*P < .01, ^**P < .001). (B) The complete set of primary cells analyzed as detailed (which also includes a number of samples that could exclusively be evaluated after coculture with BMSCs) arranged according to antitumor activity of nutlin-3a in coculture with BMSCs (•). The majority of samples was responsive to nutlin-3a treatment even in the presence of BMSCs. Weak effects sometimes reflected p53 mutation (eg, samples no. 4 and 12), and the functional status of p53 remained untested in other cases (eg, samples no. 3, 9, and 10). Nutlin-mediated cell death of certain tumor isolates was clearly less pronounced in coculture with BMSCs (samples no. 5, 8, and 11). Data for the nutlin-3b control in medium supplemented with IL-6 (essentially similar to the values in coculture; panel A; Table 2), was omitted for clarity.