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1. J Cancer Res Clin Oncol. 2012 Feb 23. [Epub ahead of print]

ABCB1 genetic variation and P-glycoprotein expression/activity in a cohort of
Brazilian acute myeloid leukemia patients.

Scheiner MA, da Cunha Vasconcelos F, da Matta RR, Dal Bello Figueira R Jr, Maia

Laboratório de Hemato-Oncologia Celular e Molecular, Programa de Pesquisa em
Hemato-Oncologia Molecular, Instituto Nacional de Câncer (INCA), Praça Cruz
Vermelha 23, 6º andar, Centro, Rio de Janeiro, RJ, CEP 20230-130, Brazil.

PURPOSE: 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.

PMID: 22358301 [PubMed - as supplied by publisher]