title: hOCT1 gene expression predict for optimal response to Imatinib in Tunisian patients with chronic myeloid leukemia.
abstract: Imatinib mesylate (IM) is considered as a highly effective therapy for chronic myeloid leukemia (CML) patients. However, a minority of patients fail to achieve optimal response due to impaired bioavailability of IM. The human organic cation transporter 1 (OCT1; SLC22A1) has been reported to be the main influx transporter involved in IM uptake into CML cells. Genetic variants and/or hOCT1 expression changes may influence IM response. In this study, we aimed to investigate the impact of both hOCT1 polymorphisms located in exon 7 and hOCT1 mRNA levels on the clinical outcome in CML patients.
  
  
  
  hOCT1 expression profile was determined using the quantitative real-time polymerase chain reaction in 69 CML patients treated with IM (35 responders to IM patients and 34 IM-resistant patients), while genotyping of 69 cases and 51 controls for hOCT1 polymorphisms was performed by direct sequencing after amplification of exon7.
  
  
  
  Our results showed that the hOCT1 gene was significantly downregulated in the samples of the IM-resistant group when compared with the IM-responder group (p = 0.0211). Moreover, sequencing data show an association in all cases between the SNP 408V>M (g.1222G>A) and an intronic 8 bp (base pairs) insertion of GTAAGTTG (rs36056065) at the 3' end of exon 7. The genotype and allele distribution of the different SNPs did not differ significantly between the two groups of patients.
  
  
  
  hOCT1 mRNA expression may serve as a clinical biomarker of response to imatinib and could be useful to predict IM therapy outcome of CML patients.
authors.affiliation: Laboratory of Molecular and Cellular Hematology, Pasteur Institute of Tunis, University of Tunis El Manar, Tunis, Tunisia. benhassine.islem@gmail.com.|, 13 Place Pasteur, BP 74, 1002, Belvedere, Tunisia. benhassine.islem@gmail.com.
authors.forename: Islem
authors.initials: I
authors.lastname: Ben Hassine
authors.affiliation: Laboratory of Molecular and Cellular Hematology, Pasteur Institute of Tunis, University of Tunis El Manar, Tunis, Tunisia.
authors.forename: Hanene
authors.initials: H
authors.lastname: Gharbi
authors.affiliation: Laboratory of Molecular and Cellular Hematology, Pasteur Institute of Tunis, University of Tunis El Manar, Tunis, Tunisia.
authors.forename: Ismail
authors.initials: I
authors.lastname: Soltani
authors.affiliation: Laboratory of Molecular and Cellular Hematology, Pasteur Institute of Tunis, University of Tunis El Manar, Tunis, Tunisia.
authors.forename: Mouheb
authors.initials: M
authors.lastname: Teber
authors.affiliation: Laboratory of Molecular and Cellular Hematology, Pasteur Institute of Tunis, University of Tunis El Manar, Tunis, Tunisia.
authors.forename: Ahlem
authors.initials: A
authors.lastname: Farrah
authors.affiliation: Laboratory of Molecular and Cellular Hematology, Pasteur Institute of Tunis, University of Tunis El Manar, Tunis, Tunisia.
authors.forename: Hind
authors.initials: H
authors.lastname: Ben Hadj Othman
authors.affiliation: Laboratory of Molecular and Cellular Hematology, Pasteur Institute of Tunis, University of Tunis El Manar, Tunis, Tunisia.
authors.forename: Hassiba
authors.initials: H
authors.lastname: Amouri
authors.affiliation: Faculté de médicine de Tunis, Tunis, Tunisia.
authors.forename: Hatem
authors.initials: H
authors.lastname: Bellaaj
authors.affiliation: Faculté de médicine de Tunis, Tunis, Tunisia.
authors.forename: Rayhane Ben
authors.initials: RB
authors.lastname: Lakhal
authors.affiliation: Faculté de médicine de Tunis, Tunis, Tunisia.
authors.forename: Neila Ben
authors.initials: NB
authors.lastname: Romdhane
authors.affiliation: Laboratory of Molecular and Cellular Hematology, Pasteur Institute of Tunis, University of Tunis El Manar, Tunis, Tunisia.
authors.forename: Salem
authors.initials: S
authors.lastname: Abbes
authors.affiliation: Laboratory of Molecular and Cellular Hematology, Pasteur Institute of Tunis, University of Tunis El Manar, Tunis, Tunisia.|Faculté de médicine de Tunis, Tunis, Tunisia.
authors.forename: Samia
authors.initials: S
authors.lastname: Menif
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000483:Alleles; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D014408:Biomarkers, Tumor / Q000097:blood; D015536:Down-Regulation / Q000187:drug effects; D005091:Exons / Q000235:genetics; D005260:Female; D005838:Genotype; D006801:Humans; D000068877:Imatinib Mesylate / Q000627:therapeutic use*; D015464:Leukemia, Myelogenous, Chronic, BCR-ABL Positive / Q000188:drug therapy* / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D050811:Octamer Transcription Factor-1 / Q000096:biosynthesis* / Q000235:genetics; D011110:Polymorphism, Genetic / Q000235:genetics; D020641:Polymorphism, Single Nucleotide / Q000235:genetics; D047428:Protein Kinase Inhibitors / Q000627:therapeutic use*; D012333:RNA, Messenger / Q000096:biosynthesis / Q000235:genetics; D014416:Tunisia; D055815:Young Adult
chemical_list: D000970:Antineoplastic Agents; D014408:Biomarkers, Tumor; D050811:Octamer Transcription Factor-1; C494165:POU2F1 protein, human; D047428:Protein Kinase Inhibitors; D012333:RNA, Messenger; D000068877:Imatinib Mesylate
keywords: Chronic myeloid leukemia; Expression; Imatinib mesylate; Polymorphisms; Resistance; hOCT1