Gerov Vladimir, Gerova Daniela, Micheva Ilina, Nikolova Miglena, Pasheva Milena, Nazifova Neshe, Galunska Bistra
Clinics of Hematology, "St. Marina" University Hospital, 9010 Varna, Bulgaria.
Department of Clinical Laboratory, Faculty of Medicine, MU Varna, 9002 Varna, Bulgaria.
Cancers (Basel). 2023 Nov 24;15(23):5562. doi: 10.3390/cancers15235562.
The hallmark of multiple myeloma is myeloma related bone disease. Interactions between myeloma plasma cells (MPCs), stromal cells, and the bone marrow (BM) microenvironment play a critical role in the pathogenesis of MBD. Bone remodeling is severely dysregulated with the prevalence of osteoclast activity. We aimed to assess circulating levels of sRANKL, periostin, and osteopontin as osteoclast activators in NDMM patients at diagnosis and in the course of treatment, correlations with clinical and laboratory data, and to evaluate their potential as additional biomarkers for the assessment of MBD. The current study involved 74 subjects (41 NDMM patients, 33 controls). MBD was assessed by whole-body low-dose computed tomography. sRANKL, periostin, and osteopontin were assayed by commercial ELISA kits. At diagnosis, all tested parameters were significantly higher in NDMM patients compared to the controls ( < 0.0001), correlating with disease stage, MBD grade, and BM infiltration by MPCs. During therapy, the serum levels of all tested proteins decrease, most prominently after autologous stem cell transplantation ( < 0.0001). A significant reduction was established in patients achieving complete and very-good partial response compared to all others ( < 0.05). In conclusion, sRANKL, periostin, and osteopontin reflect MBD severity and could be promising markers for MBD monitoring and the effect of myeloma treatment.
多发性骨髓瘤的标志是骨髓瘤相关骨病。骨髓瘤浆细胞(MPCs)、基质细胞和骨髓(BM)微环境之间的相互作用在骨髓瘤相关骨病(MBD)的发病机制中起关键作用。随着破骨细胞活性的普遍存在,骨重塑严重失调。我们旨在评估初诊和治疗过程中NDMM患者循环中作为破骨细胞激活剂的sRANKL、骨膜蛋白和骨桥蛋白水平,及其与临床和实验室数据的相关性,并评估它们作为评估MBD的额外生物标志物的潜力。本研究纳入了74名受试者(41例NDMM患者,33名对照)。通过全身低剂量计算机断层扫描评估MBD。使用商用ELISA试剂盒检测sRANKL、骨膜蛋白和骨桥蛋白。在诊断时,与对照组相比,NDMM患者所有检测参数均显著更高(<0.0001),与疾病分期、MBD分级和MPCs的骨髓浸润相关。在治疗期间,所有检测蛋白的血清水平均下降,在自体干细胞移植后下降最为显著(<0.0001)。与所有其他患者相比,达到完全缓解和非常好的部分缓解的患者有显著降低(<0.05)。总之,sRANKL、骨膜蛋白和骨桥蛋白反映了MBD的严重程度,可能是监测MBD和骨髓瘤治疗效果的有前景的标志物。