Figure 3.
Stroma-leukemia coculture increases toxicity mediated by JAK inhibitors. (A-B) Validating the effects of ruxolitinib (A) tofacitinib (B) 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. (C) STAT3 was phosphorylated in CLL cells from (n = 3) patient samples cocultured with HS-5 cells. STAT3 phosphorylation could be reversed by inhibition with ruxolitinib or tofacitinib. (D) STAT3 was phosphorylated in CLL cells from (n = 3) patient samples in the presence of conditioned medium derived from stromal cells. Ctrl, solvent control (DMSO); H, cocultures with HS-5 cells; M1-4, cocultures with MSC cells from (n = 4) different healthy donors; Ru, ruxolitinib (10 μM); To, tofacitinib (22.5 μM).

Stroma-leukemia coculture increases toxicity mediated by JAK inhibitors. (A-B) Validating the effects of ruxolitinib (A) tofacitinib (B) 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. (C) STAT3 was phosphorylated in CLL cells from (n = 3) patient samples cocultured with HS-5 cells. STAT3 phosphorylation could be reversed by inhibition with ruxolitinib or tofacitinib. (D) STAT3 was phosphorylated in CLL cells from (n = 3) patient samples in the presence of conditioned medium derived from stromal cells. Ctrl, solvent control (DMSO); H, cocultures with HS-5 cells; M1-4, cocultures with MSC cells from (n = 4) different healthy donors; Ru, ruxolitinib (10 μM); To, tofacitinib (22.5 μM).

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