文章：

基质细胞介导的Notch信号在CLL化疗耐药中的作用

Role of stromal cell-mediated Notch signaling in CLL resistance to chemotherapy

原文发布日期：2012-05-25

DOI: 10.1038/bcj.2012.17

类型: Original Article

开放获取: 是

英文摘要：

Stromal cells are essential components of the bone marrow (BM) microenvironment that regulate and support the survival of different tumors, including chronic lymphocytic leukemia (CLL). In this study, we investigated the role of Notch signaling in the promotion of survival and chemoresistance of human CLL cells in coculture with human BM-mesenchymal stromal cells (hBM-MSCs) of both autologous and allogeneic origin. The presence of BM-MSCs rescued CLL cells from apoptosis both spontaneously and following induction with various drugs, including Fludarabine, Cyclophosphamide, Bendamustine, Prednisone and Hydrocortisone. The treatment with a combination of anti-Notch-1, Notch-2 and Notch-4 antibodies or γ-secretase inhibitor XII (GSI XII) reverted this protective effect by day 3, even in presence of the above-mentioned drugs. Overall, our findings show that stromal cell-mediated Notch-1, Notch-2 and Notch-4 signaling has a role in CLL survival and resistance to chemotherapy. Therefore, its blocking could be an additional tool to overcome drug resistance and improve the therapeutic strategies for CLL.

摘要翻译： 

基质细胞是骨髓（BM）微环境的重要组成部分，可调节并支持多种肿瘤（包括慢性淋巴细胞白血病，CLL）的生存。在本研究中，我们探讨了Notch信号在骨髓间充质基质细胞（hBM-MSCs）与人CLL细胞共培养中，对CLL细胞存活和化疗耐药性的促进作用，hBM-MSCs来源包括自体和异体。BM-MSCs的存在可阻止CLL细胞自发及经氟达拉滨、环磷酰胺、苯达莫司汀、泼尼松和氢化可的松等多种药物诱导后的凋亡。使用抗Notch-1、Notch-2和Notch-4抗体组合或γ-分泌酶抑制剂XII（GSI XII）处理，即使在上述药物存在的情况下，也能在第3天逆转这种保护效应。总体而言，我们的研究结果显示，基质细胞介导的Notch-1、Notch-2和Notch-4信号在CLL细胞存活及化疗耐药中发挥作用，因此阻断该信号可能成为克服耐药、改善CLL治疗策略的额外手段。

原文链接：

Role of stromal cell-mediated Notch signaling in CLL resistance to chemotherapy