title: MDR1/ABCB1 gene polymorphisms in patients with chronic myeloid leukemia.
abstract: BACKGROUND
  Tyrosine kinase inhibitors (TKIs) are the recommended treatment for patients with chronic myeloid leukemia (CML). The MDR1/ABCB1 gene plays a role in resistance to a wide spectrum of drugs, including TKIs. However, the association of MDR1/ABCB1 gene polymorphisms (SNPs) such as C1236T, G2677T/A, and C3435T with the clinical therapeutic evolution of CML has been poorly studied. We investigated these gene polymorphisms in CML-patients treated with imatinib, nilotinib and/or dasatinib.
  
  
  METHODS
  ABCB1-SNPs were studied in 22 CML-patients in the chronic phase (CP) and 2 CML-patients in blast crisis (BC), all of whom were treated with TKIs, and compared with 25 healthy controls using nested-PCR and sequencing techniques.
  
  
  RESULTS
  Seventeen different haplotypes were identified: 7 only in controls, 6 only in CML-patients, and the remaining 4 in both groups. The distribution ratios of homozygous TT-variants present on each exon between controls and CML-patients were 2.9 for exon 12, and 0.32 for the other 2 exons. Heterozygous T-variants were observed in all controls (100%) and 75% of CML-patients. Wt-haplotype (CC-GG-CC) was observed in 6 CML-patients (25%). In this wt-group, two were treated with nilotinib and reached a major molecular response. The remaining 4 cases had either a minimal or null molecular response, or developed bone marrow aplasia.
  
  
  CONCLUSIONS
  Our results suggest that SNPs of the MDR1/ABCB1 gene could help to characterize the prognosis and the clinical-therapeutic evolution of CML-patients treated with TKIs. Wt-haplotype could be associated with a higher risk of developing CML, and a worse clinical-therapeutic evolution.
authors.affiliation: INFIBIOC-FFyB-UBA, Buenos Aires, Argentina.
authors.forename: Mabel
authors.initials: M
authors.lastname: Lardo
authors.affiliation: División Gastroenterología Hospital de Clínicas "J. San Martin", Buenos Aires, Argentina.
authors.forename: Marcelo
authors.initials: M
authors.lastname: Castro
authors.affiliation: División Hematología, Hospital Municipal "Ramos Mejía", Buenos Aires, Argentina.
authors.forename: Beatriz
authors.initials: B
authors.lastname: Moiraghi
authors.affiliation: División Hematología, Hospital de Clínicas "J. San Martin", Facultad de Medicina-UBA, Buenos Aires, Argentina.
authors.forename: Francisca
authors.initials: F
authors.lastname: Rojas
authors.affiliation: INFIBIOC-FFyB-UBA, Buenos Aires, Argentina.
authors.forename: Natalia
authors.initials: N
authors.lastname: Borda
authors.affiliation: INFIBIOC-FFyB-UBA, Buenos Aires, Argentina. ; División Hemoterapia, Hospital de Clínicas "J. San Martin", Facultad de Medicina-UBA, Buenos Aires, Argentina.
authors.forename: Jorge A
authors.initials: JA
authors.lastname: Rey
authors.affiliation: INFIBIOC-FFyB-UBA, Buenos Aires, Argentina. ; Fundación Investigar, Buenos Aires, Argentina.
authors.forename: Alberto
authors.initials: A
authors.lastname: Lazarowski
keywords: ABCB1; BCR-ABL; CML; SNPs; TKIs