Department of Internal Medicine I, University Hospital Carl Gustav Carus, Technical University of Dresden, Fetscherstraße 74, 01307, Dresden, Germany.
Department of Internal Medicine, Division of Immunotherapy and Gene Therapy, José Carreras Research Centre, Saarland University Medical Centre, Homburg, Saar, Germany.
Ann Hematol. 2020 Sep;99(9):2173-2180. doi: 10.1007/s00277-020-04163-7. Epub 2020 Jul 3.
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.
耐药性仍然是急性髓系白血病（AML）治疗的主要障碍。因此，影响治疗反应的个体遗传变异越来越受到重视。SNP 和 ABC 转运体基因都已经与耐药性相关。在这里，我们报告了 MRP1（ABCC1）SNP rs129081、rs212090 和 rs212091 的等位基因变异，这些变异对 AML 患者的生存有显著影响。在诊断时从骨髓样本中提取 DNA（n=160）。使用实时 PCR 对 7 个不同的 ABC 转运体基因中的 48 个 SNP 进行基因分型，发现 rs129081 GG 变体的 OS（p=0.035）和 DFS（p=0.01）显著升高。比较 TT 和 AA rs212090 变体，DFS 有显著影响（p=0.021）。SNP rs212091 GG 表达与 OS 较差相关（p=0.006），等位基因 GG 和 AA 之间的 DFS 差异显著（p=0.018）。多变量模型证实 rs212091 对 OS 有显著影响（AA HR=0.296，95%CI 0.113-0.774，p=0.013，GG p=0.044）。rs129081 变体 CG、rs212090 的 TT、rs212091 的 AA 和 AG 对 DFS 有显著影响（p=0.024、p=0.029、p=0.017 和 p=0.042）。该分析表明 MRP1 SNP 对 AML 患者的生存有显著影响。由于它们与预后特征无关，我们认为这些 SNP 是 AML 的独立预后标志物。
