Sawamura M, Murakami H, Tsuchiya J
National Nishigunma Hospital, Shibukawa, Gunma, Japan.
Leuk Lymphoma. 1996 Mar;21(1-2):31-6. doi: 10.3109/10428199609067576.
Multiple myeloma is a B-cell malignancy characterized by the accumulation of a clonal population of plasma cells in the bone marrow that secrete a monoclonal immunoglobulin protein. It has been regarded as a tumor arising at the B, pre-B lymphocyte, or even stem cell level. Precursor cells are presumed to proliferate and differentiate, giving rise to clonal expansion in plasma cells. Peripheral blood mononuclear cells (PBMC) from 36 patients with multiple myeloma, 12 with monoclonal gammopathy of undetermined significance (MGUS), and 21 healthy controls were cultured in vitro in the presence of tumor necrosis factor-alpha (TNF-alpha) and interleukin 4 (IL-4). We have demonstrated that monoclonal plasma cells can be induced in different proportions from PBMC obtained from myeloma patients when exposed in vitro to TNF-alpha and IL-4. Although myeloma cell precursors cannot be distinguished from other cells by morphology, a high number of monoclonal plasma cells was detected in our culture system on day 4 even when plasma cells accounted for less than 0.2% of the cells seeded on day 0. In 16 of the 36 patients with myeloma, monoclonal plasma cells appeared after 4 days. These changes were not observed in PBMC from patients with MGUS or from controls. These findings thus suggest that circulating myeloma cell precursors differentiate into plasma cells in the presence of TNF-alpha and IL-4, and the variation in the number of myeloma cell precursors in peripheral blood could therefore be used as a prognostic parameter in response to chemotherapy in myeloma patients.
多发性骨髓瘤是一种B细胞恶性肿瘤，其特征是骨髓中克隆性浆细胞群体积聚，这些浆细胞分泌单克隆免疫球蛋白。它被认为是起源于B细胞、前B淋巴细胞甚至干细胞水平的肿瘤。推测前体细胞增殖并分化，导致浆细胞克隆性扩增。将36例多发性骨髓瘤患者、12例意义未明的单克隆丙种球蛋白病（MGUS）患者和21名健康对照者的外周血单个核细胞（PBMC）在肿瘤坏死因子-α（TNF-α）和白细胞介素4（IL-4）存在的情况下进行体外培养。我们已经证明，当骨髓瘤患者的PBMC在体外暴露于TNF-α和IL-4时，可以诱导出不同比例的单克隆浆细胞。虽然骨髓瘤细胞前体无法通过形态与其他细胞区分，但即使在第0天接种的细胞中浆细胞占比不到0.2%，在第4天我们的培养系统中也检测到了大量单克隆浆细胞。在36例骨髓瘤患者中的16例中，4天后出现了单克隆浆细胞。MGUS患者或对照者的PBMC中未观察到这些变化。因此，这些发现表明，循环中的骨髓瘤细胞前体在TNF-α和IL-4存在的情况下分化为浆细胞，外周血中骨髓瘤细胞前体数量的变化因此可作为骨髓瘤患者化疗反应的一个预后参数。
