Figure 5
Figure 5. LDK is active against primary patient samples without toxicity to hematopoietic progenitors. (A-D) LDK decreases viability and induces G2/M block in primary Ph+ B-ALL patient samples. Left side of each panel shows MTT test of LDK dose-response viability assay at 48 hours incubation, n = 3, error bars = SD. Right side of each panel shows cell cycle profile for primary patient samples treated for 12 hours with DMSO, 10μM LDK, and 3μM nocodazole, n values as indicated, error bars = SEM. (E-H) LDK decreases viability of Ph+ CML and B-ALL primary leukemias without toxicity to hematopoietic stem/progenitor cells (HSPCs). (E) Cytokine-dependent methylcellulose colony formation (mean ± SD) of CML-CP (CP indicates chronic phase) with wild-type BCR-ABL (patient ID no. 10-003, black bars) and T315I mutated BCR-ABL (patient ID no. 11-007, gray bars), either untreated or treated with the indicated inhibitors. (F) Trypan blue viability assay of mononuclear cells from 3 Ph+ B-ALL patient samples treated with the indicated inhibitors. Samples 11-008 and 11-032 are paired samples from the same patient at diagnosis and relapse, respectively. (G) Cytokine-dependent methylcellulose colony formation (mean ± SD) of normal bone marrow mononuclear cells, treated with either DMSO or LDK at the indicated concentrations. (H) MTT viability assay of CD34+ HSPCs from human cord blood, treated with LDK at the indicated concentrations, relative to vehicle control. Error bars = SD Additional primary patient sample characteristics may be found in supplemental Table 5.

LDK is active against primary patient samples without toxicity to hematopoietic progenitors. (A-D) LDK decreases viability and induces G2/M block in primary Ph+ B-ALL patient samples. Left side of each panel shows MTT test of LDK dose-response viability assay at 48 hours incubation, n = 3, error bars = SD. Right side of each panel shows cell cycle profile for primary patient samples treated for 12 hours with DMSO, 10μM LDK, and 3μM nocodazole, n values as indicated, error bars = SEM. (E-H) LDK decreases viability of Ph+ CML and B-ALL primary leukemias without toxicity to hematopoietic stem/progenitor cells (HSPCs). (E) Cytokine-dependent methylcellulose colony formation (mean ± SD) of CML-CP (CP indicates chronic phase) with wild-type BCR-ABL (patient ID no. 10-003, black bars) and T315I mutated BCR-ABL (patient ID no. 11-007, gray bars), either untreated or treated with the indicated inhibitors. (F) Trypan blue viability assay of mononuclear cells from 3 Ph+ B-ALL patient samples treated with the indicated inhibitors. Samples 11-008 and 11-032 are paired samples from the same patient at diagnosis and relapse, respectively. (G) Cytokine-dependent methylcellulose colony formation (mean ± SD) of normal bone marrow mononuclear cells, treated with either DMSO or LDK at the indicated concentrations. (H) MTT viability assay of CD34+ HSPCs from human cord blood, treated with LDK at the indicated concentrations, relative to vehicle control. Error bars = SD Additional primary patient sample characteristics may be found in supplemental Table 5.

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