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https://hdl.handle.net/2440/79010
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Type: | Journal article |
Title: | Dasatinib targets chronic myeloid leukemia-CD34⁺ progenitors as effectively as it targets mature cells |
Other Titles: | Dasatinib targets chronic myeloid leukemia-CD34(+) progenitors as effectively as it targets mature cells |
Author: | Hiwase, D. Saunders, V. Nievergall, E. Ross, D. White, D. Hughes, T. |
Citation: | Haematologica: the hematology journal, 2013; 98(6):896-900 |
Publisher: | Ferrata Storti Foundation |
Issue Date: | 2013 |
ISSN: | 0390-6078 1592-8721 |
Statement of Responsibility: | Devendra K. Hiwase, Verity A. Saunders, Eva Nievergall, Douglas D. Ross, Deborah L. White, and Timothy P. Hughes |
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. |
Keywords: | Leukocytes, Mononuclear Cells, Cultured Humans Pyrimidines Thiazoles ATP-Binding Cassette Transporters Neoplasm Proteins Fusion Proteins, bcr-abl Antineoplastic Agents Antigens, CD34 Protein Kinase Inhibitors Substrate Specificity Neoplastic Stem Cells Leukemia, Myelogenous, Chronic, BCR-ABL Positive Dasatinib ATP Binding Cassette Transporter, Subfamily G, Member 2 ATP Binding Cassette Transporter, Subfamily B ATP Binding Cassette Transporter, Subfamily B, Member 1 |
Rights: | ©2013 Ferrata Storti Foundation |
DOI: | 10.3324/haematol.2012.070268 |
Published version: | http://dx.doi.org/10.3324/haematol.2012.070268 |
Appears in Collections: | Aurora harvest Medicine publications |
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