Figure 3
Figure 3. Hsp90 is a therapeutic target for B-ALL induced by BCR-ABL-T315I. (A) Treatment with the Hsp90 inhibitor IPI-504 prolonged survival of mice with B-ALL induced by BCR-ABL-T315I (right panel) but not by BCR-ABL-WT (left panel). B-ALL mice treated with a placebo (n = 9 for BCR-ABL-WT; n = 8 for BCR-ABL-T315I), imatinib (n = 8 for BCR-ABL-WT; n = 10 for BCR-ABL-T315I), IPI-504 (n = 13 for BCR-ABL-WT; n = 8 for BCR-ABL-T315I), and combination of imatinib and IPI-504 (n = 10 for BCR-ABL-WT; n = 8 for BCR-ABL-T315I). (B) Flow cytometric evaluation of the leukemic process in IPI-504– or imatinib-treated mice with B-ALL induced by BCR-ABL-WT (left panel) or BCR-ABL-T315I (right panel). The number of circulating leukemic cells (calculated as percentage of B220+ GFP+ cells × white blood cell count) in B-ALL mice treated with placebo, imatinib, IPI-504, or the combination of imatinib and IPI-504 was determined on days 11, 14, and 17 after transplantation. (C) Spleen weights of B-ALL mice treated with placebo, imatinib, IPI-504, and combination of imatinib and IPI-504. (Left panel) BCR-ABL-WT. (Right panel) BCR-ABL-T315I.

Hsp90 is a therapeutic target for B-ALL induced by BCR-ABL-T315I. (A) Treatment with the Hsp90 inhibitor IPI-504 prolonged survival of mice with B-ALL induced by BCR-ABL-T315I (right panel) but not by BCR-ABL-WT (left panel). B-ALL mice treated with a placebo (n = 9 for BCR-ABL-WT; n = 8 for BCR-ABL-T315I), imatinib (n = 8 for BCR-ABL-WT; n = 10 for BCR-ABL-T315I), IPI-504 (n = 13 for BCR-ABL-WT; n = 8 for BCR-ABL-T315I), and combination of imatinib and IPI-504 (n = 10 for BCR-ABL-WT; n = 8 for BCR-ABL-T315I). (B) Flow cytometric evaluation of the leukemic process in IPI-504– or imatinib-treated mice with B-ALL induced by BCR-ABL-WT (left panel) or BCR-ABL-T315I (right panel). The number of circulating leukemic cells (calculated as percentage of B220+ GFP+ cells × white blood cell count) in B-ALL mice treated with placebo, imatinib, IPI-504, or the combination of imatinib and IPI-504 was determined on days 11, 14, and 17 after transplantation. (C) Spleen weights of B-ALL mice treated with placebo, imatinib, IPI-504, and combination of imatinib and IPI-504. (Left panel) BCR-ABL-WT. (Right panel) BCR-ABL-T315I.

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