Role of chemokines and their receptors in chronic lymphocytic leukemia Function in microenvironment and targeted therapy

被引:32
作者
Han, Ting-Ting [1 ]
Fan, Lei [1 ]
Li, Jian-Yong [1 ]
Xu, Wei [1 ]
机构
[1] Nanjing Med Univ, Affiliated Hosp 1, Dept Hematol, Jiangsu Prov Hosp, Nanjing, Jiangsu, Peoples R China
基金
中国国家自然科学基金;
关键词
chronic leukemia lymphoma; microenvironment; chemokines; chemokines receptors; targeted therapy; B-CELL RECEPTOR; TYROSINE KINASE INHIBITOR; IN-VITRO; NODE MICROENVIRONMENT; GROWTH-FACTOR; PHASE-II; CXCR4; ACTIVATION; SURVIVAL; PCI-32765;
D O I
10.4161/cbt.26607
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
Chemokines produced in distinct tissue microenvironments sustain migration of mature lymphocytes in lymphoglandula. Chemokine receptors expressed on chronic lymphocytic leukemia (CLL) cells regulate the migration of the leukemia cells within the bone marrow (BM), lymphoid organs in collaboration with chemokines. Chemokines form a pro-survival circuitry by regulating leukocyte trafficking, maintaining extended lymphocyte survival. Therefore, chemokines in tumor cell-microenvironment interactions represent a target for treatment of CLL. AMD3100 disrupts the CLL/microenvironment interactions and influences CXCL12/CXCR4 survival signaling. Fostamatinib, ibrutinib, GS-1101 as B-cell receptor (BCR) related kinase inhibitors inhibit BCR- and chemokine-receptor-signal-regulated kinase and have a good clinical response in CLL. Lenalidomide, sorafenib, and dasatinib are other additional drugs associated with chemokine in microenvironment. Inhibiting signaling through chemokine and microenvironment associated signaling are emerging as innovative therapeutic targets in CLL. In this article, we reviewed the role of chemokines in CLL microenvironment and novel therapeutics targeting CLL microenvironment.
引用
收藏
页码:3 / 9
页数:7
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