文章：

B细胞受体和微环境在慢性淋巴细胞白血病中的作用

Role of the B-cell receptor and the microenvironment in chronic lymphocytic leukemia

原文发布日期：2013-09-20

DOI: 10.1038/bcj.2013.45

类型: Review

开放获取: 是

英文摘要：

Despite significant progress in treatment, chronic lymphocytic leukemia (CLL) remains an incurable disease. Advances have been made to understand the molecular pathogenesis underlying CLL progression and treatment resistance. We here review the available evidences concerning the role of the B-cell receptor (BCR) and the tumor microenvironment interactions in CLL pathogenesis. Antigen likely has a key role in the selection of the tumoral clone, the mutational status of immunoglobulin genes is a strong prognostic predictor and BCR signaling has been postulated to have a role for CLL trafficking and interaction with the stromal microenvironment. There is also important evidence, favoring a role for the microenvironment in CLL pathogenesis. Most, if not all, proliferative events occur in the lymph nodes and bone marrow, where leukemic cells receive through microenvironment interactions survival signals aiming to avoid apoptosis and acquire favorable tumoral growing conditions. In addition, the tumoral microenvironment appears to be the site where the acquisition of additional genetic lesions in the clone occur, which should greatly influence clinical outcome. The advent of new tyrosine kinase inhibitors which seem to be able to modulate microenvironment interactions and circumvent the p53 deletion have generated significant promise by raising the possibility that they could provide significant progress in disease treatment.

摘要翻译： 

尽管治疗取得重大进展，慢性淋巴细胞白血病（CLL）仍是一种无法治愈的疾病。在理解CLL进展和治疗抵抗背后的分子发病机制方面已取得进展。本文综述了B细胞受体（BCR）与肿瘤微环境相互作用在CLL发病机制中的相关证据：抗原可能对肿瘤克隆的选择具有关键作用，免疫球蛋白基因的突变状态是重要的预后预测指标，BCR信号传导被证实参与CLL的细胞迁移及与基质微环境的相互作用。还有重要证据表明微环境在CLL发病机制中发挥作用。绝大多数增殖事件（若非全部）发生在淋巴结和骨髓中，白血病细胞通过微环境相互作用获得生存信号以逃避凋亡，并获取有利的肿瘤生长条件。此外，肿瘤微环境似乎是克隆获得额外遗传损伤的场所，这会极大影响临床结局。新型酪氨酸激酶抑制剂的出现为疾病治疗带来重要希望，这类药物似乎能够调节微环境相互作用并规避p53基因缺失，可能推动疾病治疗取得重大进展。

原文链接：

Role of the B-cell receptor and the microenvironment in chronic lymphocytic leukemia