Figure 2.

Stroma-mediated modulation of compound efficacy. (A) Shown is the percental drug response change in coculture relative to monoculture (alias effect size) summarized by drug class (refer to “Materials and methods”). An effect size of 100% equals a doubling of the normalized viability in coculture vs monoculture. A t test was further used to compare normalized viabilities in coculture vs monoculture. Only differences with a false discovery rate ≤0.01 are highlighted as indicated. A total number of 81 or 17 samples are shown for CLL or AML, respectively. (B-C) Validating the effect of fludarabine 0.6 μM (B) and JQ-1 1.5 μM (C) from the HS-5 coculture screen (n = 81) in cocultures of CLL with primary MSCs (n = 3). t tests were used to compare the coculture mean with the reference value in monoculture. MSC1, MSC2, and MSC3 were derived from (n = 3) different healthy donors.