Hiwase, D.Saunders, V.Nievergall, E.Ross, D.White, D.Hughes, T.2013-08-012013-08-012013Haematologica: the hematology journal, 2013; 98(6):896-9000390-60781592-8721http://hdl.handle.net/2440/79010Dasatinib 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.en©2013 Ferrata Storti FoundationLeukocytes, MononuclearCells, CulturedHumansPyrimidinesThiazolesATP-Binding Cassette TransportersNeoplasm ProteinsFusion Proteins, bcr-ablAntineoplastic AgentsAntigens, CD34Protein Kinase InhibitorsSubstrate SpecificityNeoplastic Stem CellsLeukemia, Myelogenous, Chronic, BCR-ABL PositiveDasatinibATP Binding Cassette Transporter, Subfamily G, Member 2ATP Binding Cassette Transporter, Subfamily BATP Binding Cassette Transporter, Subfamily B, Member 1Journal article002012884010.3324/haematol.2012.0702680003198998000162-s2.0-8487844153319239Hiwase, D. [0000-0002-6666-3056]White, D. [0000-0003-4844-333X]Hughes, T. [0000-0002-0910-3730] [0000-0002-7990-4509]