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

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Abstract

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.

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Acknowledgments

We thank Dr. Claudete Klumb for critical reading of the article. This study was supported by the research grants from Instituto Nacional de Ciência e Tecnologia para Controle do Câncer, Conselho Nacional de Pesquisa 573806/2008-0, Fundação de Amparo a Pesquisa do Estado do Rio de Janeiro EE26/170.026/2008, FAPERJ-PPSUS, CNPq, and Programa de Oncobiologia (Fundação do Câncer/Universidade Federal do Rio de Janeiro).

Conflict of interest

The authors declare no conflict of interest related to the publication of this manuscript.

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Authors and Affiliations

  1. 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

    Marcos Antonio Mauricio Scheiner, Flavia da Cunha Vasconcelos, Roberta Rodrigues da Matta & Raquel Ciuvalschi Maia

  2. Serviço de Hematologia, Hospital do Câncer I, INCA, Rio de Janeiro, RJ, Brazil

    Reinaldo Dal Bello Figueira Jr. & Raquel Ciuvalschi Maia

Authors
  1. Marcos Antonio Mauricio Scheiner
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  2. Flavia da Cunha Vasconcelos
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  3. Roberta Rodrigues da Matta
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  4. Reinaldo Dal Bello Figueira Jr.
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  5. Raquel Ciuvalschi Maia
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Correspondence to Raquel Ciuvalschi Maia.

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Scheiner, M.A.M., da Cunha Vasconcelos, F., da Matta, R.R. et al. ABCB1 genetic variation and P-glycoprotein expression/activity in a cohort of Brazilian acute myeloid leukemia patients. J Cancer Res Clin Oncol 138, 959–969 (2012). https://doi.org/10.1007/s00432-012-1170-x

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