Inhibition of Hsp90 by IPI-504 preferentially reduces growth of myeloid leukemic cells harboring the BCR-ABL-T315I mutant. (A) Bone marrow cells from C57BL/6-Ly5.2 mice were transduced by BCR-ABL-WT, and bone marrow cells from C57BL/6-Ly5.1 mice were transduced by BCR-ABL-T315I. The transduced cells were 1:1 mixed, and 0.5 × 10⁶ mixed cells were injected into each recipient mouse (C57BL/6-Ly5.2). The mice were treated with a placebo (n = 10), imatinib (100 mg/kg, twice a day) (n = 10), and IPI-504 (50 mg/kg, once every 2 days) (n = 10), respectively, beginning at 8 days after BMT. At days 12 and 15 after BMT, GFP⁺ cells viable cells in peripheral blood of the mice were analyzed for Gr-1⁺Ly5.1⁺ cells that represented BCR-ABL-T315I–expressing myeloid cells. Gr-1⁺Ly5.1⁻ cells represented BCR-ABL-WT–expressing myeloid cells. Percentages of BCR-ABL-T315I–expressing myeloid cells in peripheral blood of IPI-504–treated CML mice were further analyzed at days 21 and 28 after BMT. The FACS results for one representative mouse from each treatment group were shown. IPI-504 but not imatinib significantly prolonged survival of the CML mice. (B) Simultaneous inhibition of Hsp90 and BCR-ABL kinase activity with IPI-504 and imatinib significantly prolongs survival of CML mice carrying both T315-expressing and WT-BCR-ABL leukemia cells. BALB/c mice were used to induce CML, and each treatment group had 10 mice.