Role of CXCR4 in the progression and therapy of acute leukaemia,Cell Proliferation

当前位置： X-MOL 学术 › Cell Prolif. › 论文详情

Our official English website, www.x-mol.net, welcomes your feedback! (Note: you will need to create a separate account there.)

Role of CXCR4 in the progression and therapy of acute leukaemia
Cell Proliferation ( IF 5.9 ) Pub Date : 2021-05-29 , DOI: 10.1111/cpr.13076
Long Su _{1,

2,

3,

4} , Zheng Hu _{1,

2} , Yong-Guang Yang _{1,

2,

3}

Affiliation

CXCR4 is expressed on leukaemia cells and haematopoietic stem cells (HSCs), and its ligand stromal-derived factor 1 (SDF-1) is produced abundantly by stromal cells in the bone marrow (BM). The SDF-1/CXCR4 axis plays important roles in homing to and retention in the protective BM microenvironment of malignant leukaemia cells and normal HSCs. CXCR4 expression is regulated by multiple mechanisms and the level of CXCR4 expression on leukaemia cells has prognostic indications in patients with acute leukaemia. CXCR4 antagonists can mobilize leukaemia cells from BM to circulation, which render them effectively eradicated by chemotherapeutic agents, small molecular inhibitors or hypomethylating agents. Therefore, such combinational therapies have been tested in clinical trials. However, new evidence emerged that drug-resistant leukaemia cells were not affected by CXCR4 antagonists, and the migration of certain leukaemia cells to the leukaemia niche was independent of SDF-1/CXCR4 axis. In this review, we summarize the role of CXCR4 in progression and treatment of acute leukaemia, with a focus on the potential of CXCR4 as a therapeutic target for acute leukaemia. We also discuss the potential value of using CXCR4 antagonists as chemosensitizer for conditioning regimens and immunosensitizer for graft-vs-leukaemia effects of allogeneic haematopoietic stem cell transplantation.

中文翻译：

CXCR4在急性白血病进展和治疗中的作用

CXCR4 在白血病细胞和造血干细胞 (HSC) 上表达，其配体基质衍生因子 1 (SDF-1) 由骨髓 (BM) 中的基质细胞大量产生。SDF-1/CXCR4 轴在恶性白血病细胞和正常 HSC 的保护性 BM 微环境中发挥重要作用。CXCR4 表达受多种机制调控，白血病细胞上 CXCR4 的表达水平对急性白血病患者具有预后指征。CXCR4 拮抗剂可以将白血病细胞从 BM 动员到循环中，这使得它们可以被化学治疗剂、小分子抑制剂或低甲基化剂有效地根除。因此，此类联合疗法已在临床试验中进行了测试。然而，新的证据表明，耐药性白血病细胞不受 CXCR4 拮抗剂的影响，某些白血病细胞向白血病生态位的迁移与 SDF-1/CXCR4 轴无关。在这篇综述中，我们总结了 CXCR4 在急性白血病的进展和治疗中的作用，重点是 CXCR4 作为急性白血病治疗靶点的潜力。我们还讨论了使用 CXCR4 拮抗剂作为预处理方案的化学增敏剂和同种异体造血干细胞移植的移植物抗白血病效应的免疫增敏剂的潜在价值。重点关注 CXCR4 作为急性白血病治疗靶点的潜力。我们还讨论了使用 CXCR4 拮抗剂作为预处理方案的化学增敏剂和同种异体造血干细胞移植的移植物抗白血病效应的免疫增敏剂的潜在价值。重点关注 CXCR4 作为急性白血病治疗靶点的潜力。我们还讨论了使用 CXCR4 拮抗剂作为预处理方案的化学增敏剂和同种异体造血干细胞移植的移植物抗白血病效应的免疫增敏剂的潜在价值。

更新日期：2021-07-02

点击分享查看原文

点击收藏

公开下载

阅读更多本刊最新论文本刊介绍/投稿指南11