多发性骨髓瘤患者骨髓CD38＋CD138＋浆细胞Notchl表达水平及其临床意义研究

Expression and clinical significance of Notchl on the membrane of bone marrow CD38＋CD138＋ plas- ma cells in the patients with multiple myeloma

目的研究多发性骨髓瘤（MM）患者骨髓CD38＋CD138＋浆细胞表面Notchl的表达水平及其临床意义，探讨Notch信号通路在MM发生、发展中的作用。方法应用流式细胞术检测33例MM患者（其中初治24例，复治9例）骨髓CD38＋CD138＋浆细胞、CD38＋CD138＋浆细胞以及15名健康对照者骨髓CD38＋CD138＋浆细胞表面Notchl表达水平，并与其他临床指标进行相关性分析。结果Notchl在MM患者CD38＋CD138＋浆细胞表达率为（60．21±25．06）％，明显高于MM患者CD38＋CD138＋浆细胞[（39．844-18．94）％，P=0．000]及正常对照组CD38＋CD138＋浆细胞[（38．34±19．39）％，P=0．004]，而后两者比较差异无统计学意义（P〉0．05）。24例初治患者CD38＋CD138＋浆细胞Notchl表达水平分别与骨髓中恶性浆细胞所占比例（r=0．914，P=0．000）、血清LDH水平（r=0．604，P=0．002）和血清β2-微球蛋白水平（r=0．455，P=0．026）呈显著正相关；而其中肾功能异常者CD38＋CD138＋浆细胞Notchl表达水平与血肌酐水平呈正相关（r=0．664，P=0．026）；与有无骨骼损害无显著相关。Notchl在CD38＋CD138＋浆细胞中的表达水平与经1个疗程VD（硼替佐米＋地塞米松）方案治疗后骨髓中恶性浆细胞下降率呈显著正相关（r=0．842，P=0．000）。结论MM患者骨髓CD38＋CD138＋浆细胞表面Notchl表达水平明显高于其在MM患者和正常人骨髓CD38＋CD138＋浆细胞膜表面的表达水平，表达水平高的骨髓瘤细胞，对早期化疗较为敏感，并与疾病的进展和预后呈现一定相关性。

Objective To investigate the expression of Notchl on the membrane of bone marrow CD38＋CD138＋ plasma cells in the patients with multiple myeloma （MM）, and explore the importance of Notch signaling pathway in the formation and progression of MM. Methods Thirty three MM patients and 15 healthy controls were enrolled in this study. The expression of Notchl on the membrane of bone marrow CD38＋CD138＋ and CD38＋CD138- plasma cells were analyzed by flow cytometry. The clinical data of MM patients were also analyzed. Results The ratio of Notchl on the membrane of CD38＋CD138＋ plasma cells of MM patients was （60.21 ±25.06）% which was significantly higher than those of CD38＋CD138- plasma cells of MM patients （ 39.84± 18.94 ） % （ P = 0. 000 ） and controls （ 38.34 ±19.39 ） % （ P = 0. 004 ）. There was no statistical difference between the two latter groups（ P 〉 0.05 ）. The expression of Notehl on CD38＋CD138＋ plasma cells from 24 newly diagnosed MM patients was correlated to the level of malignant plasma cells in there bone marrow（ r = 0. 914 ,P = 0.000） , serum level of lactate dehydrogenase（LDH） （ r = 0. 754, P =0. 007）,and 152-MG（r =0. 716, P = 0. 013）. The ratio of Notchl on the membrane of CD38＋CD138＋ plasma cells of MM patients who had renal dysfunction was correlated to their abnormal serum creatinine levels. The expression of Notehl on CD38＋CD138＋ plasma cells from 17 MM patients who received VD （bortezamib and dexamethasone） chemotherapy was correlated to the ratio of plasma cell reduction after the first VD chemotherapy （r = 0. 842,P = 0.000）. Conclusion The expression of Notchl on the membrane of CD38＋CD138＋ plasma cells of MM patients was significantly higher than those of CD38 ＋ CD138 - plasma cells of MM patients and controls. Notehl overexpressed plasma cells were sensitive to the early VD therapy, and correlated to the progression and long term outcome of MM.