CHU Montpellier, Institute of Research in Biotherapy, Hopital St Eloi, Av. Augustin Fliche, Montpellier Cedex 5, France.
Exp Hematol. 2010 Dec;38(12):1189-1198.e3. doi: 10.1016/j.exphem.2010.09.002. Epub 2010 Sep 18.
Multiple myeloma is a plasma cell neoplasm characterized by the accumulation of malignant plasma cells within the bone marrow. This disease remains incurable despite major treatment improvements. However, gene expression profiling of multiple myeloma cells (MMC) may lead to identification of new therapeutic targets.
Using Affymetrix microarrays, we identified the overexpression of the MYEOV gene in MMC of 171 patients with newly diagnosed multiple myeloma compared to normal plasma cells.
The MYEOV gene was present (Affymetrix call) in 79% of MMC and in 15% of normal plasma cells. MYEOV gene is not expressed in cells of the patients' bone marrow environment. The downregulation of MYEOV gene reduced the growth of a MYEOV(present) myeloma cell line, unlike a MYEOV(absent) one. Patients with MYEOV(absent) MMC have an increased event-free survival compared to patients with MYEOV(present) MMC, after high-dose therapy and stem cell transplantation and a trend for increased overall survival. In a Cox proportional hazard model, MYEOV expression in MMC is predictive for event-free survival for patients independently of International Staging System stage, t(4;14) translocation, albumin, or B2M serum levels. A knockout of MYEOV significantly reduced the growth of MMC.
Thus, MYEOV expression is a prognostic factor for patients with multiple myeloma, in part through a role of MYEOV in the control of MMC proliferation.
多发性骨髓瘤是一种浆细胞瘤，其特征是恶性浆细胞在骨髓内积聚。尽管治疗方法有了重大改进，但这种疾病仍然无法治愈。然而，多发性骨髓瘤细胞（MMC）的基因表达谱分析可能会导致新的治疗靶点的发现。
我们使用 Affymetrix 微阵列，比较了 171 例新诊断多发性骨髓瘤患者与正常浆细胞的 MMC，发现 MYEOV 基因表达过度。
MYEOV 基因在 79%的 MMC 中存在（Affymetrix 调用），在 15%的正常浆细胞中存在。MYEOV 基因不在患者骨髓环境中的细胞中表达。与 MYEOV(缺失)骨髓瘤细胞系相比，下调 MYEOV 基因会降低 MYEOV(存在)骨髓瘤细胞系的生长。与 MYEOV(存在)MMC 患者相比，在接受高剂量治疗和干细胞移植后，MYEOV(缺失)MMC 患者无事件生存时间延长，且总体生存时间有延长趋势。在 Cox 比例风险模型中，MMC 中的 MYEOV 表达独立于国际分期系统分期、t(4;14)易位、白蛋白或 B2M 血清水平，是预测无事件生存的预后因素。MYEOV 的敲除显著降低了 MMC 的生长。
因此，MYEOV 表达是多发性骨髓瘤患者的预后因素，部分原因是 MYEOV 在控制 MMC 增殖中的作用。
