Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Letter to the Editor
  • Published:

Positive impact of ABCB1 polymorphisms in overall survival and complete remission in acute myeloid leukemia: a systematic review and meta-analysis

The Pharmacogenomics Journal volume 16, pages 1–2 (2016)Cite this article

Subjects

We recently conducted a systematic review and meta-analysis of seven cohort studies (1241 patients) that evaluated the association between ABCB1 polymorphisms 1236C>T, 2677G>T/A and 3435C>T and effectiveness variables in acute myeloid leukemia (AML) treatment.1 In the last months, two large cohort studies in AML patients that analyzed these ABCB1 polymorphisms were published.2, 3 One of them is an extension of a preceding study4 that we included in our meta-analysis, and now it has increased the number of patients to 201 and has conducted a subgroup analysis based on FLT3 and NPM1 status. The other study has evaluated ABCB1 genotypes and haplotypes in 263 AML de novo Chinese Han adult patients. Both studies met the inclusion criteria of our meta-analysis and they will be included if we had made the systematic search today. We re-analyzed our data including these studies and we obtained similar results in overall survival (OS), the variant allele of all three studied ABCB1 single nucleotide polymorphisms significantly increased OS (Table 1).

Table 1 Summary of ORs with 95% CIs for ordinary genetic contrasts of the association between the ABCB1 1236C>T, 2677G>T/A and 3435C>T polymorphisms and OS/CR with fixed effects
Full size table

The most significant change that we observed in our new analysis was related with complete remission (CR). Our previous analysis and other meta-analysis5 did not find association between ABCB1 genotypes and CR. However, our new analysis that duplicates the number of patients, showed that variant allele of 1236C>T and 2677G>T/A displayed significantly higher CR (Table 1). These findings reinforce the impact of ABCB1 variants in AML induction therapy and explain that our earlier results found a trend that has been confirmed in our following analysis by increasing the sample size.

This is a preview of subscription content, access via your institution

Access options

Buy this article

  • Purchase on Springer Link
  • Instant access to full article PDF
Buy now

Prices may be subject to local taxes which are calculated during checkout

References

  1. Megías-Vericat JE, Rojas L, Herrero MJ, Bosó V, Montesinos P, Moscardó F et al. Influence of ABCB1 polymorphisms upon the effectiveness of standard treatment for acute myeloid leukemia: A systematic review and meta-analysis of observational studies. Pharmacogenomics J 2015; 15: 109–118.

    Article  PubMed  Google Scholar 

  2. Jakobsen Falk I, Fyrberg A, Paul E, Nahi H, Hermanson M, Rosenquist R et al. Impact of ABCB1 single nucleotide polymorphisms 1236C>T and 2677G>T on overall survival in FLT3 wild-type de novo AML patients with normal karyotype. Br J Haematol 2014; 167: 671–680.

    Article  CAS  PubMed  Google Scholar 

  3. He H, Yin J, Li X, Zhang Y, Xu X, Zhai M et al. Association of ABCB1 polymorphisms with prognostic outcomes of anthracycline and cytarabine in Chinese patients with acute myeloid leukemia. Eur J Clin Pharmacol 2015; 71: 293–302.

    Article  CAS  PubMed  Google Scholar 

  4. Gréen H, Falk IJ, Lotfi K, Paul E, Hermansson M, Rosenquist R et al. Association of ABCB1 polymorphisms with survival and in vitro cytotoxicty in de novo acute myeloid leukemia with normal karyotype. Pharmacogenomics J 2012; 12: 111–118.

    Article  PubMed  Google Scholar 

  5. Doxani C, Voulgarelis M, Zintzaras E . MDR1 mRNA expression and MDR1 gene variants as predictors of response to chemotherapy in patients with acute myeloid leukaemia: a meta-analysis. Biomarkers 2013; 18: 425–435.

    Article  CAS  PubMed  Google Scholar 

  6. Hur EH, Lee JH, Lee MJ, Choi SJ, Lee JH, Kang MJ et al. C3435T polymorphism of the MDR1 gene is not associated with P-glycoprotein function of leukemic blasts and clinical outcome in patients with acute myeloid leukemia. Leuk Res 2008; 32: 1601–1604.

    Article  CAS  PubMed  Google Scholar 

  7. Kim DH, Park JY, Sohn SK, Lee NY, Baek JH, Jeon SB et al. Multidrug resistance-1 gene polymorphisms associated with treatment outcomes in de novo acute myeloid leukemia. Int J Cancer 2006; 118: 2195–2201.

    Article  CAS  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Unidad de Farmacogenética, Instituto Investigación Sanitaria La Fe and Área del Medicamento, Hospital Universitario y Politécnico La Fe, Valencia, Spain

    J E Megías-Vericat, L Rojas, M J Herrero, V Bosó & S F Aliño

  2. Servicio de Farmacia, Área del Medicamento, Hospital Universitario y Politécnico La Fe, Valencia, Spain

    J E Megías-Vericat, V Bosó & J L Poveda

  3. Department of Internal Medicine, Faculty of Medicine, Pontificia Universidad Católica de Chile, Santiago, Chile

    L Rojas

  4. Departamento Farmacología, Facultad de Medicina, Universidad de Valencia, Valencia, Spain

    M J Herrero & S F Aliño

  5. Servicio de Hematología y Hemoterapia, Hospital Universitario y Politécnico La Fe, Valencia, Spain

    P Montesinos, F Moscardó & M A Sanz

  6. Unidad de Farmacología Clínica, Área del Medicamento, Hospital Universitario y Politécnico La Fe, Valencia, Spain

    S F Aliño

Authors
  1. J E Megías-Vericat
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. L Rojas
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. M J Herrero
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. V Bosó
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. P Montesinos
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. F Moscardó
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. J L Poveda
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. M A Sanz
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. S F Aliño
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding authors

Correspondence to J E Megías-Vericat or M J Herrero.

Ethics declarations

Competing interests

The authors declare no conflict of interest.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Megías-Vericat, J., Rojas, L., Herrero, M. et al. Positive impact of ABCB1 polymorphisms in overall survival and complete remission in acute myeloid leukemia: a systematic review and meta-analysis. Pharmacogenomics J 16, 1–2 (2016). https://doi.org/10.1038/tpj.2015.79

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/tpj.2015.79

This article is cited by

Search

Advanced search

Quick links