Babak Myeloma Group, Department of Pathophysiology, Faculty of Medicine, Masaryk University, 625 00 Brno, Czech Republic.
Centre for Molecular Medicine, Central European Institute of Technology, Masaryk University, 625 00 Brno, Czech Republic.
Int J Mol Sci. 2022 Nov 25;23(23):14765. doi: 10.3390/ijms232314765.
Extramedullary multiple myeloma (EMD) is an aggressive disease; malignant plasma cells lose their dependence in the bone marrow microenvironment and migrate into tissues. EMD is a negative prognostic factor of survival. Using flow cytometry and next-generation sequencing, we aimed to identify antigens and microRNAs (miRNAs) involved in EMD pathogenesis. Flow cytometry analysis revealed significant differences in the level of clonal plasma cells between MM and EMD patients, while the expression of CD markers was comparable between these two groups. Further, miR-26a-5p and miR-30e-5p were found to be significantly down-regulated in EMD compared to MM. Based on the expression of miR-26a-5p, we were able to distinguish these two groups of patients with high sensitivity and specificity. In addition, the involvement of deregulated miRNAs in cell cycle regulation, ubiquitin-mediated proteolysis and signaling pathways associated with infections or neurological disorders was observed using GO and KEGG pathways enrichment analysis. Subsequently, a correlation between the expression of analyzed miRNAs and the levels of CD molecules was observed. Finally, clinicopathological characteristics as well as CD antigens associated with the prognosis of MM and EMD patients were identified. Altogether, we identified several molecules possibly involved in the transformation of MM into EMD.
髓外多发性骨髓瘤（EMD）是一种侵袭性疾病；恶性浆细胞失去对骨髓微环境的依赖并迁移到组织中。EMD 是生存的负预后因素。我们使用流式细胞术和下一代测序，旨在鉴定参与 EMD 发病机制的抗原和 microRNAs（miRNAs）。流式细胞术分析显示 MM 和 EMD 患者之间克隆浆细胞的水平存在显著差异，而这两组之间的 CD 标志物表达相当。此外，与 MM 相比，EMD 中 miR-26a-5p 和 miR-30e-5p 的表达明显下调。基于 miR-26a-5p 的表达，我们能够以高灵敏度和特异性区分这两组患者。此外，使用 GO 和 KEGG 途径富集分析观察到失调 miRNA 参与细胞周期调控、泛素介导的蛋白水解和与感染或神经紊乱相关的信号通路。随后观察到分析的 miRNA 表达与 CD 分子水平之间的相关性。最后，确定了与 MM 和 EMD 患者预后相关的临床病理特征以及 CD 抗原。总之，我们鉴定了几个可能参与 MM 向 EMD 转化的分子。
