Sokołowski Marcin, Łacina Piotr, Bogunia-Kubik Katarzyna, Mazur Grzegorz, Butrym Aleksandra
Dr Alfred Sokolowski Specialist Hospital in Walbrzych, 58-309 Wałbrzych, Poland.
Lower Silesian Oncology, Pulmonology and Hematology Center, 53-314 Wroclaw, Poland.
Int J Mol Sci. 2025 May 29;26(11):5237. doi: 10.3390/ijms26115237.
Multiple myeloma is a neoplastic disease characterised by the proliferation of clonal, atypical plasma cells. In cancer cells, the balance between two paths of cell death, necroptosis and apoptosis, is disrupted. The aim of this study was to analyse the occurrence of polymorphisms in genes encoding key proteins for the necroptosis process, i.e., RIPK-1, RIPK-3 and MAPKAPK2. We investigated the potential relations between the occurrence of genetic variability and the clinical course of the disease. We analysed six single-nucleotide polymorphisms in a population of patients with multiple myeloma ( = 205) and healthy volunteers ( = 100): RIPK1 rs2272990, RIPK1 rs9391981, RIPK3 rs724165, RIPK3rs3212243, MAPKAPK2, rs45514798 and MAPKAPK2 rs4073250. We found that genotypes rs9391981 CG, rs724165 CG, rs3212243 GG, and rs4073250 AA were independent predictors of overall survival, while genotype MAPKAPK2 rs4073250 AA was an independent predictor of progression-free survival. MAPKAPK2 rs45514798 AA was associated with polyneuropathy after thalidomide therapy. In conclusion, some of the SNPs tested have potential prognostic value and could be used as marker of survival in patients with multiple myeloma.
多发性骨髓瘤是一种以克隆性、非典型浆细胞增殖为特征的肿瘤性疾病。在癌细胞中，细胞死亡的两条途径——坏死性凋亡和凋亡之间的平衡被打破。本研究的目的是分析坏死性凋亡过程关键蛋白编码基因，即RIPK-1、RIPK-3和MAPKAPK2中多态性的发生情况。我们研究了基因变异性的发生与疾病临床进程之间的潜在关系。我们分析了多发性骨髓瘤患者群体（n = 205）和健康志愿者群体（n = 100）中的六个单核苷酸多态性：RIPK1 rs2272990、RIPK1 rs9391981、RIPK3 rs724165、RIPK3 rs3212243、MAPKAPK2 rs45514798和MAPKAPK2 rs4073250。我们发现基因型rs9391981 CG、rs724165 CG、rs3212243 GG和rs4073250 AA是总生存期的独立预测指标，而基因型MAPKAPK2 rs4073250 AA是无进展生存期的独立预测指标。MAPKAPK2 rs45514798 AA与沙利度胺治疗后的多发性神经病相关。总之，所检测的一些单核苷酸多态性具有潜在的预后价值，可作为多发性骨髓瘤患者生存的标志物。
