Ribatti Domenico, Vacca Angelo
Department of Basic Medical Sciences, Neurosciences and Sensory Organs, Section of Human Anatomy and Histology, University of Bari Medical School "Aldo Moro", Piazza G. Cesare, 11, 70124, Bari, Italy.
National Cancer Institute, Giovanni Paolo II, Bari, Italy.
Cancer Treat Res. 2016;169:51-61. doi: 10.1007/978-3-319-40320-5_5.
Multiple myeloma (MM) mainly progresses in bone marrow (BM). Therefore, signals from the BM microenvironment are thought to play a critical role in maintaining plasma cell growth, migration, and survival. Reciprocal positive and negative interactions between plasma cells and microenvironmental cells, including endothelial cells (ECs) and fibroblasts may occur. The BM neovascularization is a constant hallmark of MM, and goes hand in hand with progression to leukemic phase. Microenvironmental factors induce MMECs and fibroblasts to become functionally different from monoclonal gammopathy of undetermined significance (MGUS) ECs (MGECs), i.e., to acquire an overangiogenic phenotype, and be similar to transformed cells. These alterations play an important role in MM progression and may represent new molecular markers for prognostic stratification of patients and prediction of response to antiangiogenic drugs, as well as new potential therapeutic targets.
多发性骨髓瘤（MM）主要在骨髓（BM）中进展。因此，来自骨髓微环境的信号被认为在维持浆细胞生长、迁移和存活中起关键作用。浆细胞与包括内皮细胞（ECs）和成纤维细胞在内的微环境细胞之间可能发生相互的正负相互作用。骨髓新生血管形成是MM的一个持续特征，并与向白血病期的进展密切相关。微环境因素诱导MMECs和成纤维细胞在功能上不同于意义未明的单克隆丙种球蛋白病（MGUS）的ECs（MGECs），即获得过度血管生成表型，并类似于转化细胞。这些改变在MM进展中起重要作用，可能代表患者预后分层和抗血管生成药物反应预测的新分子标志物，以及新的潜在治疗靶点。
