title: Low ABCB1 and high OCT1 levels play a favorable role in the molecular response to imatinib in CML patients in the community clinical practice.
abstract: Despite the favorable clinical evolution of patients with chronic myeloid leukemia (CML), resistance or intolerance to imatinib is present in approximately 35% of patients. Sokal score is a widely used risk factor, however efflux and influx transporters are provisional risk factors implicated in imatinib resistance. This study analyzed Sokal score, ABCB1, ABCG2 and OCT1 mRNA transporter expression levels as well as P-glycoprotein expression and efflux transporters activity to seek a possible correlation between these factors and the molecular response at 12 months from imatinib start as well as 8-year overall survival (OS). Low plus intermediate Sokal score correlated to optimal imatinib responses, as well as OS at 8-years, thus confirming the established role of Sokal score as a prognostic factor in CML patients. Low ABCB1 and high OCT1 mRNA levels were associated with an optimal molecular response, while the inverse levels were associated with non-responders (warning and failure) patients. Our results suggest that ABCB1 and OCT1 mRNA expressions may present biological relevance to identify responder and non-responder patients to imatinib treatment.
authors: Laboratório de Hemato-Oncologia Celular e Molecular, Programa de Pesquisa em Hemato-Oncologia Molecular, Coordenação de Pesquisa, Instituto Nacional de Câncer (INCA), RJ, Brazil.
authors: Flavia
authors: F
authors: da Cunha Vasconcelos
authors: Laboratório de Hemato-Oncologia Celular e Molecular, Programa de Pesquisa em Hemato-Oncologia Molecular, Coordenação de Pesquisa, Instituto Nacional de Câncer (INCA), RJ, Brazil.
authors: Marcos Antonio
authors: MA
authors: Mauricio Scheiner
authors: Serviço de Hematologia, INCA, RJ, Brazil.
authors: Arthur
authors: A
authors: Moellman-Coelho
authors: Departamento de Biofísica e Biometria Roberto Alcântara Gomes, Instituto de Biologia, Universidade do Estado do Rio de Janeiro (UERJ), RJ, Brazil.
authors: André Luiz
authors: AL
authors: Mencalha
authors: Laboratório de Biologia Molecular, Centro de Transplante de Medula Óssea, (CEMO), INCA, RJ, Brazil.
authors: Ilana Zalcberg
authors: IZ
authors: Renault
authors: Laboratório de Imunologia Tumoral, Instituto de Bioquímica Médica Leopoldo de Meis, Universidade Federal do Rio de Janeiro (UFRJ), Centro de Ciências da Saúde, RJ, Brazil.
authors: Vivian Mary
authors: VM
authors: Rumjanek
authors: Laboratório de Hemato-Oncologia Celular e Molecular, Programa de Pesquisa em Hemato-Oncologia Molecular, Coordenação de Pesquisa, Instituto Nacional de Câncer (INCA), RJ, Brazil; Serviço de Hematologia, INCA, RJ, Brazil. Electronic address: rcmaia@inca.gov.br.
authors: Raquel Ciuvalschi
authors: RC
authors: Maia
mesh_terms: D018435:ATP Binding Cassette Transporter, Subfamily B / Q000097:blood / Q000235:genetics; D000070997:ATP Binding Cassette Transporter, Subfamily G, Member 2 / Q000097:blood; D000293:Adolescent; D000328:Adult; D000368:Aged; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D019008:Drug Resistance, Neoplasm; D005260:Female; D006764:Hospitals, Community; D006801:Humans; D000068877:Imatinib Mesylate / Q000627:therapeutic use*; D015464:Leukemia, Myelogenous, Chronic, BCR-ABL Positive / Q000175:diagnosis / Q000188:drug therapy* / Q000401:mortality; D008297:Male; D008875:Middle Aged; D027702:Organic Cation Transporter 1 / Q000235:genetics*; D011379:Prognosis; D012333:RNA, Messenger / Q000097:blood*; D012074:Remission Induction; D012307:Risk Factors; D015996:Survival Rate; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: C513055:ABCB1 protein, human; D018435:ATP Binding Cassette Transporter, Subfamily B; D000070997:ATP Binding Cassette Transporter, Subfamily G, Member 2; D000970:Antineoplastic Agents; D027702:Organic Cation Transporter 1; D012333:RNA, Messenger; D000068877:Imatinib Mesylate
keywords: ABCB1/P-glycoprotein; ABCG2; Chronic myeloid leukemia; Imatinib; OCT1; Sokal score