PDF(Pubmed)
Abstract：
UNASSIGNED: The hallmark of multiple myeloma (MM) is a clonal plasma cell infiltration in the bone marrow accompanied by myelosuppression and osteolysis. Premalignant stages such as monoclonal gammopathy of undetermined significance (MGUS) and asymptomatic stages such as smoldering myeloma (SMM) can progress to MM. Mesenchymal stromal cells (MSCs) are an integral component of the bone marrow microenvironment and play an important role in osteoblast differentiation and hematopoietic support. Although stromal alterations have been reported in MM contributing to hematopoietic insufficiency and osteolysis, it is not clear whether alterations in MSC already occur in MGUS or SMM. In this study, we analyzed MSCs from MGUS, SMM, and MM regarding their properties and functionality and performed messenger RNA sequencing to find underlying molecular signatures in different disease stages. A high number of senescent cells and a reduced osteogenic differentiation capacity and hematopoietic support were already present in MGUS MSC. As shown by RNA sequencing, there was a broad spectrum of differentially expressed genes including genes of the BMP/TGF-signaling pathway, detected already in MGUS and that clearly increases in patients with SMM and MM. Our data may help to block these signaling pathways in the future to hinder progression to MM.
摘要：
多发性骨髓瘤（MM）的标志是骨髓中的克隆浆细胞浸润，伴有骨髓抑制和骨质溶解。癌前阶段，如未确定意义的单克隆丙种球蛋白病（MGUS）和无症状阶段，如闷烧性骨髓瘤（SMM），可发展为多发性骨髓瘤（MM）。间充质基质细胞（MSC）是骨髓微环境的组成部分，在成骨细胞分化和造血支持中起重要作用。虽然据报道MM中的基质改变会导致造血功能不全和骨质溶解，尚不清楚MSC的改变是否已经在MGUS或SMM中发生。在这项研究中，我们分析了来自MGUS的MSC，SMM和MM对它们的特性和功能进行了mRNA测序，以发现不同疾病阶段的潜在分子特征。在MGUSMSC中已经存在大量衰老细胞和降低的成骨分化能力和造血支持。如RNA测序所示，存在广泛的差异表达基因，包括BMP/TGF信号通路的基因，已经在MGUS中检测到，并且在SMM和MM患者中明显增加。我们的数据可能有助于在未来阻断这些信号通路，以阻碍多发性骨髓瘤的进展。
