title: Pretherapeutic expression of the hOCT1 gene predicts a complete molecular response to imatinib mesylate in chronic-phase chronic myeloid leukemia.
abstract: In this retrospective study we evaluated the pretherapeutic mRNA expression of the hOCT1 (human organic cation transporter 1) gene in patients with chronic-phase (CP) chronic myeloid leukemia (CML) who varied in terms of their response to imatinib (IM). hOCT1 mRNA was quantiﬁed by real-time PCR. Patients were classified as expressing either high (n = 44) or low hOCT1 mRNA (n = 44). The complete cytogenetic response rates observed at 6, 12 and 18 months were 47.7, 84.1 and 91%, respectively, in patients with high hOCT1 mRNA and 47.5, 81.8 and 86.3%, respectively, in patients with low hOCT1 transcripts. The major molecular response rates were not significantly different between patients with high and low hOCT1 mRNA after 6 months of therapy (22.7 vs. 9.1%; p = 0.07), but they were significantly different after 12 months (54.5 vs. 31.8%; p = 0.026) and 18 months (77.2 vs. 56.8%; p = 0.034). Complete molecular responses were observed in 5 patients with low and 17 patients with high hOCT1 mRNA (p = 0.003). The 5-year event-free and overall survival analyses revealed no significant differences between the groups. These data imply that knowledge of the pretherapeutic level of hOCT1 could be a useful marker to predict IM therapy outcome in treatment-naïve CP CML patients.
authors.affiliation: Tumor Biology Laboratory, Faculty of Medicine, University of São Paulo, Brazil.
authors.forename: Luciana
authors.initials: L
authors.lastname: Nardinelli
authors.forename: Sabri Saeed
authors.initials: SS
authors.lastname: Sanabani
authors.forename: Alline
authors.initials: A
authors.lastname: Didone
authors.forename: Patricia de Barros
authors.initials: Pde B
authors.lastname: Ferreira
authors.forename: Mariana
authors.initials: M
authors.lastname: Serpa
authors.forename: Mafalda Megumi Yoshinaga
authors.initials: MM
authors.lastname: Novaes
authors.forename: Mariana
authors.initials: M
authors.lastname: Marchiani
authors.forename: Antonio Lancha
authors.initials: AL
authors.lastname: Ruiz
authors.forename: Ismael Severino
authors.initials: IS
authors.lastname: Lima
authors.forename: Dalton de Alencar Fischer
authors.initials: Dde A
authors.lastname: Chamone
authors.forename: Israel
authors.initials: I
authors.lastname: Bendit
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D001549:Benzamides; D014408:Biomarkers, Tumor / Q000235:genetics; D018572:Disease-Free Survival; D005260:Female; D015870:Gene Expression; D006801:Humans; D000068877:Imatinib Mesylate; D053208:Kaplan-Meier Estimate; D015466:Leukemia, Myeloid, Chronic-Phase / Q000188:drug therapy* / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D027702:Organic Cation Transporter 1 / Q000235:genetics*; D010879:Piperazines / Q000627:therapeutic use*; D011743:Pyrimidines / Q000627:therapeutic use*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D012334:RNA, Neoplasm / Q000235:genetics / Q000378:metabolism; D060888:Real-Time Polymerase Chain Reaction; D012074:Remission Induction; D012189:Retrospective Studies; D013997:Time Factors; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: D000970:Antineoplastic Agents; D001549:Benzamides; D014408:Biomarkers, Tumor; D027702:Organic Cation Transporter 1; D010879:Piperazines; D011743:Pyrimidines; D012333:RNA, Messenger; D012334:RNA, Neoplasm; D000068877:Imatinib Mesylate