American Society of Hematology

Figure 4

$Figure 4. Chloroquine selectively augments the anticancer activity of SAHA in imatinib-refractory primary CML cells. (A) Effects of CQ, SAHA, and the combination on the overall growth and viability of peripheral-blood mononuclear cells (PBMCs) from healthy donors (n = 2) and primary cells from imatinib-refractory patients (n = 5). Cells were treated with 25 μM CQ, 2 μM SAHA, or the combination for 48 hours. Effects on overall growth and viability were determined by MTT assays. Error bars indicate the SEM. (B) Quantification of drug-induced apoptosis in PBMCs from healthy donors (n = 2) and primary CML cells from imatinib-refractory patients (n = 5). Cells were treated with 25 μM CQ, 2 μM SAHA, or the combination for 48 hours. Drug-induced apoptosis was determined by PI/FACS. Error bars indicate the SEM. (C) Prolonged effects of CQ, SAHA, and the combination on the clonogenic survival of normal bone marrow versus CML cells. Primary bone marrow cells harvested from C57BL/6J mice and K562 and LAMA 84 CML cells were treated for 24 hours with 25 μM CQ, 2 μM SAHA, and the combination. Cells were washed twice in PBS and plated in cytokine-free Methocult medium. The Methocult for murine bone marrow cells was supplemented with 20 units/mL IL-3. Colonies from K562 and LAMA 84 cells were scored after 8 days and murine bone marrow colonies were scored after 14 days in culture. n = 2; error bars represent the SEM. *P < .05.$

Chloroquine selectively augments the anticancer activity of SAHA in imatinib-refractory primary CML cells. (A) Effects of CQ, SAHA, and the combination on the overall growth and viability of peripheral-blood mononuclear cells (PBMCs) from healthy donors (n = 2) and primary cells from imatinib-refractory patients (n = 5). Cells were treated with 25 μM CQ, 2 μM SAHA, or the combination for 48 hours. Effects on overall growth and viability were determined by MTT assays. Error bars indicate the SEM. (B) Quantification of drug-induced apoptosis in PBMCs from healthy donors (n = 2) and primary CML cells from imatinib-refractory patients (n = 5). Cells were treated with 25 μM CQ, 2 μM SAHA, or the combination for 48 hours. Drug-induced apoptosis was determined by PI/FACS. Error bars indicate the SEM. (C) Prolonged effects of CQ, SAHA, and the combination on the clonogenic survival of normal bone marrow versus CML cells. Primary bone marrow cells harvested from C57BL/6J mice and K562 and LAMA 84 CML cells were treated for 24 hours with 25 μM CQ, 2 μM SAHA, and the combination. Cells were washed twice in PBS and plated in cytokine-free Methocult medium. The Methocult for murine bone marrow cells was supplemented with 20 units/mL IL-3. Colonies from K562 and LAMA 84 cells were scored after 8 days and murine bone marrow colonies were scored after 14 days in culture. n = 2; error bars represent the SEM. *P < .05.

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