摘要
慢性淋巴细胞白血病(CLL),是西方成年人中最普遍的一种白血病,特征是一个相对成熟的CD5+B细胞在周围血管、淋巴节和骨髓中逐步积累。尽管在治疗上的最近进展中,慢性淋巴细胞白血病仍然是无法治愈的。淋巴节和骨髓是保护白血病细胞防止自发性或药物诱导凋亡的避难所,在这些区域白细胞的浸润与临床分期和预测有关。在疾病中微生物环境所扮演的主要角色成为了增加清晰度。不同的趋化因子(CXCL12, CXCL13, CCL19, CCL21)可能事实上参与了吸引慢性淋巴细胞白血病细胞进入骨髓和淋巴节,在那里各种因素,像IL-15 和CXCL12,增强了白血病细胞的存活度。最近,我们建议肝细胞生长因子(HGF),它由微生物环境基质细胞所生产,为慢性淋巴细胞白血病病理研究做贡献。我们阐明肝细胞生长因子运用在CLLB细胞的双重影响,通过与其受体C的相互作用满足;HGF,事实上,保护CLL B细胞,这是c-Met +,细胞凋亡,并使单核/巨噬细胞向M2表型,从而促进CLL克隆逃避免疫控制。这些双重影响通过两种主要信号通路活性调解:STAT3TYR705 and AKT。这篇综述的主要目的是总结HGF数据和c-MET在普通B细胞和B细胞恶性肿瘤的表达,我们强调在CLL中存在的结果。总之,这里描述的观点建议HGF/c-MET axis可能在恶性肿瘤中扮演重要的角色,最新的潜在治疗方案旨在阻止HGF诱导在B淋巴组织增生性疾病的信号通路。
关键词: B淋巴组织增生性疾病,HGF,c-MET,免疫抑制,生存,治疗靶点。
Current Molecular Medicine
Title:Survival and Immunosuppression Induced by Hepatocyte Growth Factor in Chronic Lymphocytic Leukemia
Volume: 17 Issue: 1
关键词: B淋巴组织增生性疾病,HGF,c-MET,免疫抑制,生存,治疗靶点。
摘要: Chronic lymphocytic leukemia (CLL), the most common leukemia among adults in the western world, is characterized by a progressive accumulation of relatively mature CD5+ B cells in peripheral blood, lymph nodes and bone marrow. Despite much recent advancement in therapy, CLL is still incurable. Lymph nodes and bone marrow represent sanctuary sites preserving leukemic cells from spontaneous or drug-induced apoptosis, and infiltration of leukemic cells in these districts correlates with clinical stages and prognosis. The central role played by the microenvironment in the disease has become increasingly clear. Different chemokines (CXCL12, CXCL13, CCL19, CCL21) may in fact participate in attracting CLL cells into bone marrow and lymph nodes, where various factors, such as IL-15 and CXCL12, enhance leukemic cells survival. Recently, we have suggested that hepatocyte growth factor (HGF), produced by microenvironmental stromal cells, can contribute to CLL pathogenesis. We have demonstrated that HGF exerts a double effect on CLL B cells through the interaction with its receptor c- MET; HGF, infact, protects CLL B cells, which are c-MET+, from apoptosis, and also polarizes mono/macrophages towards the M2 phenotype, thus facilitating the evasion of the CLL clone from immune control. This double effect appears mediated by the activation of two major signaling pathways: STAT3TYR705 and AKT. The aim of this review is to summarize data on HGF and c-MET expression in normal B cells and in B cell malignancies, with a particular emphasis on our results obtained in CLL. Altogether, the observations described here suggest that the HGF/c-MET axis may have a prominent role in malignancy progression further indicating novel potential therapeutic options aimed to block HGF-induced signaling pathways in B lymphoproliferative disorders.
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Survival and Immunosuppression Induced by Hepatocyte Growth Factor in Chronic Lymphocytic Leukemia, Current Molecular Medicine 2017; 17 (1) . https://dx.doi.org/10.2174/1566524017666170220095838
DOI https://dx.doi.org/10.2174/1566524017666170220095838 |
Print ISSN 1566-5240 |
Publisher Name Bentham Science Publisher |
Online ISSN 1875-5666 |
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