Multidrug-related protein 1 (MRP1) polymorphisms rs129081, rs212090, and rs212091 predict survival in normal karyotype a
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ORIGINAL ARTICLE
Multidrug-related protein 1 (MRP1) polymorphisms rs129081, rs212090, and rs212091 predict survival in normal karyotype acute myeloid leukemia Desiree Kunadt 1 & Christian Dransfeld 2 & Claudia Dill 1 & Maria Schmiedgen 1 & Michael Kramer 1 & Heidi Altmann 1 & Christoph Röllig 1 & Martin Bornhäuser 1 & Ulrich Mahlknecht 3 & Markus Schaich 4 & Friedrich Stölzel 1 Received: 4 May 2020 / Accepted: 21 June 2020 # The Author(s) 2020
Abstract 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. Keywords Acute myeloid leukemia . Multidrug resistance . MRP1 . SNPs . Prognosis . Survival
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Electronic supplementary material The online version of this article (https://doi.org/10.1007/s00277-020-04163-7) contains supplementary material, which is available to authorized users. * Desiree Kunadt [email protected] 1
Department of Internal Medicine I, University Hospital Carl Gustav Carus, Technical University of Dresden, Fetscherstraße 74, 01307 Dresden, Germany
2
Department of Internal Medicine, Division of Immunotherapy and Gene Therapy, José Carreras Research Centre, Saarland University Medical Centre, Homburg, Saar, Germany
3
Department of Internal Medicine Hematology/Oncology, St. Lukas Klinik, Solingen, Germany
4
Department of Hematology, Oncology and Palliative Care, Rems-Murr-Klinikum, Winnenden, Germany
Acute myeloid leukemia (AML) is characterized by uncontrolled proliferation of undifferentiated myeloid blasts requiring rapid induction chemotherapy to induce a remission. Although approximately 75% of patients achieve complete remission (CR) after induction treatment consisting of cytarabine (100 mg/m2, days 1–7) and daunorubicin (60 mg
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