title: Phosphorylated Crkl reduction levels are associated with the lowest P-glycoprotein activity levels in cells from chronic myeloid leukemia patients.
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.
authors.affiliation: Laboratório de Hemato-Oncologia Celular e Molecular, Programa de Pesquisa em Hemato-Oncologia Molecular, Instituto Nacional de Câncer (INCA), Brazil.
authors.forename: Flavia Cunha
authors.initials: FC
authors.lastname: Vasconcelos
authors.forename: Gabriela
authors.initials: G
authors.lastname: Nestal de Moraes
authors.forename: Arthur
authors.initials: A
authors.lastname: Moellmann-Coelho
authors.forename: Raquel Ciuvalschi
authors.initials: RC
authors.lastname: Maia
mesh_terms: D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000378:metabolism*; D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000970:Antineoplastic Agents / Q000627:therapeutic use; D001549:Benzamides / Q000627:therapeutic use; D014408:Biomarkers, Tumor / Q000378:metabolism; D002648:Child; D002675:Child, Preschool; D019008:Drug Resistance, Neoplasm; D005260:Female; D006801:Humans; D000068877:Imatinib Mesylate; D020014:K562 Cells; D015464:Leukemia, Myelogenous, Chronic, BCR-ABL Positive / Q000175:diagnosis / Q000188:drug therapy / Q000378:metabolism* / Q000473:pathology; D061986:MCF-7 Cells; D008297:Male; D008875:Middle Aged; D010766:Phosphorylation; D010879:Piperazines / Q000627:therapeutic use; D011494:Protein Kinases / Q000378:metabolism; D050737:Proto-Oncogene Proteins c-crk / Q000378:metabolism*; D011743:Pyrimidines / Q000627:therapeutic use; D055815:Young Adult
chemical_list: D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D000970:Antineoplastic Agents; D001549:Benzamides; D014408:Biomarkers, Tumor; D010879:Piperazines; D050737:Proto-Oncogene Proteins c-crk; D011743:Pyrimidines; D000068877:Imatinib Mesylate; D011494:Protein Kinases
keywords: BCRP; Chronic myeloid leukemia; Imatinib; P-glycoprotein; p-Crkl