title: ABCB1 genetic variation and P-glycoprotein expression/activity in a cohort of Brazilian acute myeloid leukemia patients.
abstract: OBJECTIVE
  Polymorphisms in the ABCB1 gene may influence P-glycoprotein (Pgp) expression and/or activity. Because the population in Brazil is markedly heterogeneous, we analyzed the relationship between ABCB1 polymorphisms and Pgp expression/activity in Brazilian acute myeloid leukemia (AML) patients.
  
  
  METHODS
  Acute myeloid leukemia samples from 109 patients were studied. ABCB1 gene variants rs1128503 (C1236T) and rs1045643 (C3435T) were analyzed by PCR-RFLP assay. Pgp expression and Pgp activity were analyzed by flow cytometry.
  
  
  RESULTS
  There was a similar distribution of Pgp expression and activity on polymorphisms C1236T, C1236C, and T1236T for exon 12, and C3435T, C3435C, and T3435T for exon 26. An exception was observed in the lowest ratio of mean fluorescence intensity (MFI) median for Pgp expression in the TT genotype for both studied exons, and its correspondence to a low MFI median for Pgp activity. Pgp expression did not show impact on the response to remission induction therapy, but the MFI median of Pgp expression in the remission failure group was higher than that of the complete remission (CR) group of patients (p = 0.04). Overall survival (OS) was significantly influenced by CR (p = 0.0001). Better 5-year OS and 5-year event-free survival rates (p = 0.04 and p = 0.007, respectively) were achieved in patients presenting the genetic variant CC in exon 12 followed by those presenting the variant CT in exon 26 (p = 0.001).
  
  
  CONCLUSIONS
  Polymorphisms in the ABCB1 gene and the levels of Pgp expression could be useful to identify prognostic in AML patients.
authors.affiliation: Laboratório de Hemato-Oncologia Celular e Molecular, Programa de Pesquisa em Hemato-Oncologia Molecular, Instituto Nacional de Câncer, Praça Cruz Vermelha 23, 6º andar, Centro, Rio de Janeiro, RJ CEP 20230-130, Brazil.
authors.forename: Marcos Antonio Mauricio
authors.initials: MA
authors.lastname: Scheiner
authors.forename: Flavia
authors.initials: F
authors.lastname: da Cunha Vasconcelos
authors.forename: Roberta Rodrigues
authors.initials: RR
authors.lastname: da Matta
authors.forename: Reinaldo
authors.initials: R
authors.lastname: Dal Bello Figueira
authors.forename: Raquel Ciuvalschi
authors.initials: RC
authors.lastname: Maia
mesh_terms: D018435:ATP Binding Cassette Transporter, Subfamily B; D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000096:biosynthesis / Q000235:genetics* / Q000378:metabolism*; D000293:Adolescent; D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use; D001938:Brazil; D015331:Cohort Studies; D018572:Disease-Free Survival; D005091:Exons; D005260:Female; D006239:Haplotypes; D006801:Humans; D015470:Leukemia, Myeloid, Acute / Q000097:blood / Q000188:drug therapy / Q000235:genetics* / Q000378:metabolism*; D007958:Leukocyte Count / Q000379:methods; D008297:Male; D008875:Middle Aged; D011110:Polymorphism, Genetic; D012074:Remission Induction; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: C513055:ABCB1 protein, human; D018435:ATP Binding Cassette Transporter, Subfamily B; D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1