Multiple myeloma cells expressing low levels of CD138 have an immature phenotype and reduced sensitivity to lenalidomide.
Multiple myeloma cells expressing low levels of CD138 have an immature phenotype and reduced sensitivity to lenalidomide.
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DOI：
10.3892/ijo.2012.1545
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发表时间：
2012-09
影响因子：
5.2
通讯作者：
Hata H
中科院分区：
文献类型：
--
作者：
Kawano Y;Fujiwara S;Wada N;Izaki M;Yuki H;Okuno Y;Iyama K;Yamasaki H;Sakai A;Mitsuya H;Hata H
CD138 表达是浆细胞和多发性骨髓瘤细胞的标志。然而，在骨髓瘤患者的浆细胞中经常观察到 CD138 表达降低，尽管其临床意义尚不清楚。为了评估 CD138 低表达在 MM 中的意义，我们检查了表达低水平 CD138 的 MM 细胞的表型。原发性 MM 细胞的流式细胞术分析显示，与未经治疗的 MM 患者相比，复发/进展性疾病患者的 CD138 表达显着降低。在新诊断的患者和接受大剂量化疗后接受自体干细胞移植的患者中，与高水平 CD138 的患者相比，低水平 CD138 的患者总体生存率较差。两种 MM 细胞系，KYMM-1（CD138− 低）和 KYMM-2（CD138− 高），是从 CD138 表达降低的单个 MM 患者建立的。与 KYMM-2 细胞相比，在 KYMM-1 中观察到 BCL6 和 PAX5 高表达，IRF4、PRDM1 和 XBP1 下调，表明 KYMM-1 的不成熟表型。 KYMM-1 对来那度胺的敏感性低于 KYMM-2，而对硼替佐米的敏感性没有差异。使用抗 CD138 包被的磁珠将 KYMM-2 细胞进一步分为 CD138+ 和 CD138− 部分。与 CD138+ 细胞相比，从 KYMM-2 细胞系分选的 CD138− 细胞也表现出高 BCL6、低 IRF4 表达以及对来那度胺的敏感性降低。我们的观察表明，低 CD138 表达与 i) 不良预后、ii) 不成熟表型和 iii) 对来那度胺的低敏感性有关。观察到的 CD138 低 MM 细胞的独特特征表明，这应该被认为是一个新的临床实体。需要针对表达低水平 CD138 的 MM 细胞制定治疗策略，以改善其不良预后。
CD138 expression is a hallmark of plasma cells and multiple myeloma cells. However, decreased expression of CD138 is frequently observed in plasma cells of myeloma patients, although the clinical significance of this is unclear. To evaluate the significance of low expression of CD138 in MM, we examined the phenotypes of MM cells expressing low levels of CD138. Flow cytometric analysis of primary MM cells revealed a significant decrease in CD138 expression in patients with relapsed/progressive disease compared with untreated MM patients. Patients with low levels of CD138 had a worse overall survival compared with patients with high levels of CD138, in newly diagnosed patients and patients receiving high-dose chemotherapy followed by autologous stem-cell transplantation. Two MM cell lines, KYMM-1 (CD138− low) and KYMM-2 (CD138− high), were established from a single MM patient with decreased CD138 expression. High expression of BCL6 and PAX5, and downregulation of IRF4, PRDM1 and XBP1 was observed in KYMM-1 compared with KYMM-2 cells, indicative of the immature phenotype of KYMM-1. KYMM-1 was less sensitive to lenalidomide than KYMM-2, while no difference in sensitivity to bortezomib was observed. KYMM-2 cells were further divided in CD138+ and CD138− fractions using anti-CD138-coated magnetic beads. CD138− cells sorted from the KYMM-2 cell line also showed high BCL6, low IRF4 expression and decreased sensitivity to lenalidomide compared with CD138+ cells. Our observations suggest that low CD138 expression relates to i) poor prognosis, ii) immature phenotype and iii) low sensitivity to lenalidomide. The observed distinct characteristics of CD138 low MM cells, suggest this should be recognized as a new clinical entity. Establishment of a treatment strategy for MM cells expressing low levels of CD138 is needed to improve their poor outcome.
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影响因子：
20.3
作者：
Mahmoud, MS;Huang, NH;Kawano, MM
通讯作者：
Kawano, MM
影响因子：
3.7
作者：
Brennan, Sarah K.;Wang, Qiuju;Matsui, William
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影响因子：
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作者：
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Dore, JM
影响因子：
20.3
作者：
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影响因子：
11.2
作者：
Matsui, William;Wang, Qiuju;Jones, Richard J.
通讯作者：
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