Dasatinib targets chronic myeloid leukemia-CD34⁺ progenitors as effectively as it targets mature cells
Date
2013
Authors
Hiwase, D.
Saunders, V.
Nievergall, E.
Ross, D.
White, D.
Hughes, T.
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Journal article
Citation
Haematologica: the hematology journal, 2013; 98(6):896-900
Statement of Responsibility
Devendra K. Hiwase, Verity A. Saunders, Eva Nievergall, Douglas D. Ross, Deborah L. White, and Timothy P. Hughes
Conference Name
Abstract
Dasatinib is effective in most chronic phase chronic myeloid leukemia patients both in first-line therapy and following imatinib failure. While imatinib uptake into CD34(+) cells is low compared to mononuclear cells, few data evaluate how well dasatinib targets primitive CML cells. This study compares intracellular concentration of dasatinib and Bcr-Abl kinase inhibition in CML-CD34(+) progenitors and mononuclear cells induced by dasatinib. The intracellular concentrations of dasatinib were similar between CML-CD34(+) and mononuclear cells (P=0.8). Similarly, there was no significant difference in the degree of dasatinib-mediated Bcr-Abl kinase inhibition. ABCB1 (MDR1) and ABCG2 inhibitors neither increased dasatinib intracellular concentration nor enhanced dasatinib-mediated Bcr-Abl kinase inhibition. In contrast to nilotinib, we show that dasatinib is not an ABCB1 inhibitor. Thus, dasatinib targets CML-CD34(+) progenitors as effectively as it targets mononuclear cells. ABCB1 and ABCG2 efflux pumps do not appear to influence the intracellular dasatinib concentration in CML-CD34(+) progenitors.
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©2013 Ferrata Storti Foundation