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Multidrug-related protein 1 (MRP1) polymorphisms rs129081, rs212090, and rs212091 predict survival in normal karyotype acute myeloid leukemia

Resistant disease is still a main obstacle in acute myeloid leukemia (AML) treatment. Therefore, individual genetic variations affecting therapy response are gaining increasing importance. Both SNPs and ABC transporter genes could already be associated with drug resistance. Here, we report allelic v...

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Autores principales: Kunadt, Desiree, Dransfeld, Christian, Dill, Claudia, Schmiedgen, Maria, Kramer, Michael, Altmann, Heidi, Röllig, Christoph, Bornhäuser, Martin, Mahlknecht, Ulrich, Schaich, Markus, Stölzel, Friedrich
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Springer Berlin Heidelberg 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7419446/
https://www.ncbi.nlm.nih.gov/pubmed/32621177
http://dx.doi.org/10.1007/s00277-020-04163-7
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author Kunadt, Desiree
Dransfeld, Christian
Dill, Claudia
Schmiedgen, Maria
Kramer, Michael
Altmann, Heidi
Röllig, Christoph
Bornhäuser, Martin
Mahlknecht, Ulrich
Schaich, Markus
Stölzel, Friedrich
author_facet Kunadt, Desiree
Dransfeld, Christian
Dill, Claudia
Schmiedgen, Maria
Kramer, Michael
Altmann, Heidi
Röllig, Christoph
Bornhäuser, Martin
Mahlknecht, Ulrich
Schaich, Markus
Stölzel, Friedrich
author_sort Kunadt, Desiree
collection PubMed
description Resistant disease is still a main obstacle in acute myeloid leukemia (AML) treatment. Therefore, individual genetic variations affecting therapy response are gaining increasing importance. Both SNPs and ABC transporter genes could already be associated with drug resistance. Here, we report allelic variants of MRP1 (ABCC1) SNPs rs129081, rs212090, and rs212091 with significant influences on survival in AML patients. DNA was extracted from bone marrow samples (n = 160) at diagnosis. Genotyping 48 SNPs within seven different ABC transporter genes using real-time PCR revealed rs129081 GG variant with a significant higher OS (p = 0.035) and DFS (p = 0.01). Comparing TT and AA rs212090 variants showed significant influences on DFS (p = 0.021). SNP rs212091 GG expression was associated with worse OS (p = 0.006) and a significant difference in DFS between alleles GG and AA (p = 0.018). The multivariable models confirmed a significant influence on OS for rs212091 (AA HR = 0.296, 95% CI 0.113–0.774, p = 0.013 and GG p = 0.044). Rs129081 variant CG, TT of rs212090, AA, and AG of rs212091 demonstrated significant impact on DFS (p = 0.024, p = 0.029, p = 0.017, and p = 0.042, respectively). This analysis demonstrates a significant influence of MRP1 SNPs on survival in AML. As they were not associated to prognostic characteristics, we suggest these SNPs to be independent prognostic markers for AML. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1007/s00277-020-04163-7) contains supplementary material, which is available to authorized users.
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spelling pubmed-74194462020-08-18 Multidrug-related protein 1 (MRP1) polymorphisms rs129081, rs212090, and rs212091 predict survival in normal karyotype acute myeloid leukemia Kunadt, Desiree Dransfeld, Christian Dill, Claudia Schmiedgen, Maria Kramer, Michael Altmann, Heidi Röllig, Christoph Bornhäuser, Martin Mahlknecht, Ulrich Schaich, Markus Stölzel, Friedrich Ann Hematol Original Article Resistant disease is still a main obstacle in acute myeloid leukemia (AML) treatment. Therefore, individual genetic variations affecting therapy response are gaining increasing importance. Both SNPs and ABC transporter genes could already be associated with drug resistance. Here, we report allelic variants of MRP1 (ABCC1) SNPs rs129081, rs212090, and rs212091 with significant influences on survival in AML patients. DNA was extracted from bone marrow samples (n = 160) at diagnosis. Genotyping 48 SNPs within seven different ABC transporter genes using real-time PCR revealed rs129081 GG variant with a significant higher OS (p = 0.035) and DFS (p = 0.01). Comparing TT and AA rs212090 variants showed significant influences on DFS (p = 0.021). SNP rs212091 GG expression was associated with worse OS (p = 0.006) and a significant difference in DFS between alleles GG and AA (p = 0.018). The multivariable models confirmed a significant influence on OS for rs212091 (AA HR = 0.296, 95% CI 0.113–0.774, p = 0.013 and GG p = 0.044). Rs129081 variant CG, TT of rs212090, AA, and AG of rs212091 demonstrated significant impact on DFS (p = 0.024, p = 0.029, p = 0.017, and p = 0.042, respectively). This analysis demonstrates a significant influence of MRP1 SNPs on survival in AML. As they were not associated to prognostic characteristics, we suggest these SNPs to be independent prognostic markers for AML. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1007/s00277-020-04163-7) contains supplementary material, which is available to authorized users. Springer Berlin Heidelberg 2020-07-03 2020 /pmc/articles/PMC7419446/ /pubmed/32621177 http://dx.doi.org/10.1007/s00277-020-04163-7 Text en © The Author(s) 2020 Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/.
spellingShingle Original Article
Kunadt, Desiree
Dransfeld, Christian
Dill, Claudia
Schmiedgen, Maria
Kramer, Michael
Altmann, Heidi
Röllig, Christoph
Bornhäuser, Martin
Mahlknecht, Ulrich
Schaich, Markus
Stölzel, Friedrich
Multidrug-related protein 1 (MRP1) polymorphisms rs129081, rs212090, and rs212091 predict survival in normal karyotype acute myeloid leukemia
title Multidrug-related protein 1 (MRP1) polymorphisms rs129081, rs212090, and rs212091 predict survival in normal karyotype acute myeloid leukemia
title_full Multidrug-related protein 1 (MRP1) polymorphisms rs129081, rs212090, and rs212091 predict survival in normal karyotype acute myeloid leukemia
title_fullStr Multidrug-related protein 1 (MRP1) polymorphisms rs129081, rs212090, and rs212091 predict survival in normal karyotype acute myeloid leukemia
title_full_unstemmed Multidrug-related protein 1 (MRP1) polymorphisms rs129081, rs212090, and rs212091 predict survival in normal karyotype acute myeloid leukemia
title_short Multidrug-related protein 1 (MRP1) polymorphisms rs129081, rs212090, and rs212091 predict survival in normal karyotype acute myeloid leukemia
title_sort multidrug-related protein 1 (mrp1) polymorphisms rs129081, rs212090, and rs212091 predict survival in normal karyotype acute myeloid leukemia
topic Original Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7419446/
https://www.ncbi.nlm.nih.gov/pubmed/32621177
http://dx.doi.org/10.1007/s00277-020-04163-7
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