Hsp90 inhibition has differential effects on BCR-ABL degradation and Hsp70 induction in myeloid and lymphoid cells in vitro and in vivo. (A) In 32D cells, IPI-504–induced degradation of BCR-ABL-T315I was greater than that of BCR-ABL-WT. BCR-ABL-WT– or BCR-ABL-T315I–expressing 32D cells were treated with different concentrations of IPI-504 for 12 hours. Protein lysates were analyzed by Western blotting using antibodies indicated. (B) In Ba/F3 cells, IPI-504 induced significant degradation of BCR-ABL-T315I but not BCR-ABL-WT. BCR-ABL-WT– or BCR-ABL-T315I–expressing 32D cells were treated with different concentrations of IPI-504 for 12 hours. Protein lysates were analyzed by Western blotting using antibodies indicated. (C) Mice with BCR-ABL-T315I–induced CML were treated with placebo, imatinib (100 mg/kg, twice a day by gavage), and IPI-504 (50 mg/kg, once every 2 days by gavage), respectively, for 8 days, beginning at day 8 after transplantation. At 6 hours after the last dose, protein lysates of leukemic cells from the spleen of the treated CML mice were analyzed by Western blotting using antibodies indicated. The black line indicates that the lanes that were not adjacent on the same original Western blotting gel were brought together to generate this figure. (D) Mice with BCR-ABL-T315I–induced B-ALL were treated with placebo, imatinib, and IPI-504, respectively, for 8 days, beginning at day 8 after transplantation. At 6 hours after the last dose, protein lysates of leukemic cells from the spleen of the treated mice were analyzed by Western blotting using antibodies indicated. The black line indicates that the lanes that were not adjacent on the same original Western blotting gel were brought together to generate this figure.