Puthier D, Pellat-Deceunynck C, Barillé S, Robillard N, Rapp M J, Juge-Morineau N, Harousseau J L, Bataille R, Amiot M
INSERM U463 Institut de Biologie, Nantes, France.
Leukemia. 1999 Feb;13(2):289-94. doi: 10.1038/sj.leu.2401302.
Multiple myeloma (MM) is a malignancy characterized by a very slow proliferation of malignant plasma cells leading to their accumulation within the bone marrow. This suggests that resistance to apoptosis may play a critical role both in the pathogenesis and resistance to treatment of MM. Bcl-2 is a key protein for the regulation of apoptosis. However, it has been shown that this protein also regulates the state of proliferation. In the current study, we show that malignant plasma cells from both the bone marrow and peripheral blood express high levels of Bcl-2 and are slowly proliferating cells. In contrast, myeloma cells from extramedullary sites (ie pleural effusion, ascitis, mammary and gastric plasmacytoma) express Bcl-2 weakly while being highly proliferative. Normal non-dividing bone marrow plasma cells express high levels of Bcl-2 protein. In contrast, four highly proliferative reactive plasmacytosis express weak levels of Bcl-2. We conclude that there is an inverse correlation between Bcl-2 expression and the proliferation rate of both normal and malignant plasma cells. These data may be explained by the double function of Bcl-2, ie its well known function as an anti-apoptotic molecule and its intriguing function as an inhibitory molecule of cell proliferation.
多发性骨髓瘤（MM）是一种恶性肿瘤，其特征是恶性浆细胞增殖非常缓慢，导致它们在骨髓中积聚。这表明对细胞凋亡的抗性可能在MM的发病机制和对治疗的抗性中都起关键作用。Bcl-2是调节细胞凋亡的关键蛋白。然而，已经表明该蛋白还调节增殖状态。在当前研究中，我们表明来自骨髓和外周血的恶性浆细胞均表达高水平的Bcl-2，并且是缓慢增殖的细胞。相比之下，来自髓外部位（即胸腔积液、腹水、乳腺和胃浆细胞瘤）的骨髓瘤细胞Bcl-2表达较弱，同时具有高增殖性。正常非分裂骨髓浆细胞表达高水平的Bcl-2蛋白。相比之下，四种高增殖性反应性浆细胞增多症Bcl-2表达水平较弱。我们得出结论，Bcl-2表达与正常和恶性浆细胞的增殖率之间存在负相关。这些数据可以通过Bcl-2的双重功能来解释，即其作为抗凋亡分子的众所周知的功能及其作为细胞增殖抑制分子的有趣功能。
