Cives Mauro, Ciavarella Sabino, Dammacco Franco, Silvestris Franco
Department of Internal Medicine and Oncology, Section of Clinical Oncology, University of Bari "A. Moro", Bari, Italy.
Crit Rev Oncog. 2013;18(1-2):75-95. doi: 10.1615/critrevoncog.v18.i1-2.50.
Multiple myeloma (MM) is a B cell malignancy characterized by uncontrolled expansion of malignant plasma cells within the bone marrow that contribute to formation of multiple osteolytic bone disease and severe skeletal devastation. Recently, direct and indirect observations suggest that fusion events between cells housed within the MM marrow microenvironment often occur and may play a role in tumor progression, including myeloma bone disease (MBD). A number of cells resident in the marrow, such as myeloid progenitors and dendritic cells, have inherited fusogenicity and osteoclastogenic potential due to the expression of a number of fusogenic proteins as well as a high sensitivity to fusogenic factors produced within the MM marrow milieu. Similarly, osteoclasts (OC), as bone-resorbing multinucleated cells resulting from the fusion of marrow monocyte/ macrophages, have been reported to improperly fuse with malignant plasma cells and drive transition of these cells into OC-like cells exerting bone-resorbing capacity. Further, based on indirect cytogenetic and molecular evidence, it has been proposed that MM cells may generate a hybrid progeny with high metastatic potential and drug resistance, ultimately pointing to uncontrolled homotypic fusions that accelerate MBD progression.
多发性骨髓瘤（MM）是一种B细胞恶性肿瘤，其特征是骨髓内恶性浆细胞不受控制地增殖，导致多发性溶骨性骨病的形成和严重的骨骼破坏。最近，直接和间接观察表明，MM骨髓微环境中的细胞之间经常发生融合事件，并且可能在肿瘤进展中发挥作用，包括骨髓瘤骨病（MBD）。骨髓中的许多细胞，如髓系祖细胞和树突状细胞，由于多种融合蛋白的表达以及对MM骨髓环境中产生的融合因子高度敏感，而具有融合性和破骨细胞生成潜力。同样，破骨细胞（OC）作为骨髓单核细胞/巨噬细胞融合产生的骨吸收多核细胞，据报道会与恶性浆细胞异常融合，并促使这些细胞转变为具有骨吸收能力的OC样细胞。此外，基于间接的细胞遗传学和分子证据，有人提出MM细胞可能产生具有高转移潜力和耐药性的杂交后代，最终指向加速MBD进展的不受控制的同型融合。
