title: [H-oCT1 gene expression as a predictor of major and complete molecular response to imatinib of chronic myeloid leukemia. Single center experience].
abstract: Chronic myeloid leukemia is a clonal disorder caused by formation of chimeric BCR/ABL gene and bcr/abl protein with abnormally high tyrosine kinase activity. The use of imatinib--the first tyrosine kinase inhibitor results in achievement of hematologic, cytogenetic and molecular response in majority of patients. However despite its high efficacy not all patients respond to imatinib, whereas others lose an initial response. Imatinib is a substrate of human organic cation transporter-1 (hOCT1), which actively delivers the drug into the cells, and efflux transporters. To identify potential imatinib failures, we investigated the expression of hOCT1 using real-time quantitative reverse transcription-polymerase chain reaction (RQ-PCR) in 155 CML patients. Patients with low pretreatment hOCT1 expression had inferior major and complete molecular response (MMR and CMR) rates (p = 0.0001, p = 0.0001) achieved any time or at 18 months of imatinib treatment (p = 0.023, p = 0.022). The expression of hOCT1 is important in determining the clinical response to imatinib. The analysis of hOCT1 expression by RQ-PCR is convenient and clinically available, and the results could help in introduction of optimal first line therapy in CML patients.
authors.affiliation: Katedra i Klinika Hematologii, Collegium Medicum UJ w Krakowie. sachatom@gmail.com
authors.forename: Tomasz
authors.initials: T
authors.lastname: Sacha
authors.forename: Sylwia
authors.initials: S
authors.lastname: Czekalska
authors.forename: Kajetana
authors.initials: K
authors.lastname: Foryciarz
authors.forename: Magdalena
authors.initials: M
authors.lastname: Zawada
authors.forename: Izabela
authors.initials: I
authors.lastname: Florek
authors.forename: Dorota
authors.initials: D
authors.lastname: Cwynar
authors.forename: Gracjan
authors.initials: G
authors.lastname: Wator
authors.forename: Walentyna
authors.initials: W
authors.lastname: Balwierz
authors.forename: Aleksander B
authors.initials: AB
authors.lastname: Skotnicki
mesh_terms: D000328:Adult; D001549:Benzamides; D014408:Biomarkers, Tumor / Q000032:analysis*; D005260:Female; D015973:Gene Expression Regulation, Leukemic; D005819:Genetic Markers / Q000235:genetics*; D006801:Humans; D000068877:Imatinib Mesylate; D015464:Leukemia, Myelogenous, Chronic, BCR-ABL Positive / Q000175:diagnosis* / Q000188:drug therapy* / Q000235:genetics; D008297:Male; D008875:Middle Aged; D027702:Organic Cation Transporter 1 / Q000235:genetics*; D010879:Piperazines / Q000627:therapeutic use*; D047428:Protein Kinase Inhibitors / Q000627:therapeutic use*; D011743:Pyrimidines / Q000627:therapeutic use*
chemical_list: D001549:Benzamides; D014408:Biomarkers, Tumor; D005819:Genetic Markers; D027702:Organic Cation Transporter 1; D010879:Piperazines; D047428:Protein Kinase Inhibitors; D011743:Pyrimidines; D000068877:Imatinib Mesylate