Institute of Hematology and Bone Marrow Transplantation, Sourasky Medical Center, Tel Aviv, Israel.
Semin Cancer Biol. 2010 Jun;20(3):178-85. doi: 10.1016/j.semcancer.2010.07.001. Epub 2010 Jul 15.
Poor prognosis of acute leukemia with current treatments is mainly due to the relapse of the disease following chemotherapy. In the last decade, an emerging concept has proposed that the leukemia stem cells (LSCs) and their interactions with the BM microenvironment are the major cause of the acute leukemia relapse. Adhesion to the stromal niche is crucial for LSCs as it directly supports self-renewal, proliferation, arrest of differentiation and protects from damaging chemo-agents. One of the key players in this crosstalk between leukemic cells and the BM stroma niche is the chemokine SDF-1. SDF-1 regulates the process of homing and engraftment of LSCs into the BM and inhibition of its receptor CXCR4 induces leukemic cell mobilization into the circulation. However, besides its chemotactic and adhesive functions, SDF-1 is also a pleiotropic cytokine that regulates leukemic cell proliferation as well as their program of differentiation. CXCR4 antagonists are used in combination with chemotherapy in preclinical and clinical studies, which demonstrate that blocking CXCR4 is a novel promising approach of therapy. In this review, we focus on the multifaceted SDF-1/CXCR4 axis in acute leukemia and discuss how targeting this pathway could provide potential interest to eradicate the LSCs.
目前的治疗方法对急性白血病的预后较差，主要是由于化疗后疾病复发。在过去的十年中，一个新出现的概念提出，白血病干细胞（LSCs）及其与骨髓微环境的相互作用是急性白血病复发的主要原因。黏附于基质龛对于 LSCs 至关重要，因为它直接支持自我更新、增殖、阻止分化，并防止受到化学药物的损伤。在白血病细胞与骨髓基质龛之间的这种串扰中，关键参与者之一是趋化因子 SDF-1。SDF-1 调节 LSCs 归巢和植入骨髓的过程，抑制其受体 CXCR4 可诱导白血病细胞动员到循环中。然而，除了趋化和黏附功能外，SDF-1 还是一种多效细胞因子，可调节白血病细胞的增殖及其分化程序。CXCR4 拮抗剂已在临床前和临床研究中与化疗联合使用，这些研究表明阻断 CXCR4 是一种有前途的新型治疗方法。在这篇综述中，我们重点介绍急性白血病中多方面的 SDF-1/CXCR4 轴，并讨论靶向该途径如何为根除 LSCs 提供潜在的益处。
