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Phosphorylated Crkl reduction levels are associated with the lowest P-glycoprotein activity levels in cells from chronic myeloid leukemia patients
Authors:Flavia Cunha Vasconcelos  Gabriela Nestal de Moraes  Arthur Moellmann-Coelho  Raquel Ciuvalschi Maia
Affiliation:1. Laboratório de Hemato-Oncologia Celular e Molecular, Programa de Pesquisa em Hemato-Oncologia Molecular, Instituto Nacional de Câncer (INCA), Brazil;2. Programa de Pós-Graduação Stricto Sensu em Oncologia, INCA, RJ, Brazil;3. Serviço de Hematologia, Hospital do Câncer I, INCA, Brazil
Abstract:ABCB1/P-glycoprotein (Pgp) and ABCG2/BCRP overexpression have been described as related to imatinib resistance in chronic myeloid leukemia (CML). We showed in CML cells from 55 patients that Pgp activity was more frequently detected than BCRP activity (p = 0.0074). Imatinib-induced Crkl phosphorylated protein (pCrkl) reduction was more pronounced in K562 (Pgp-negative) than in K562-Lucena (Pgp-positive) CML cell line. Expressive pCrkl reduction levels after in vitro imatinib treatment was observed in samples from patients exhibiting lower Pgp activity levels compared with patients exhibiting higher Pgp activity levels (p = 0.0045). Pgp activity in association with pCrkl reduction levels might help to distinguish between imatinib-resistant and imatinib-sensitive CML cells.
Keywords:Chronic myeloid leukemia   p-Crkl   P-glycoprotein   BCRP   Imatinib
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