1st Department of Pathology and Experimental Cancer Research, Faculty of Medicine, Semmelweis University, H-1085 Üllői út 26, Budapest, Hungary.
Department of Hematology, Markusovszky University Teaching Hospital, Szombathely, Hungary.
Ann Hematol. 2018 Nov;97(11):2145-2152. doi: 10.1007/s00277-018-3410-x. Epub 2018 Jun 28.
CD49d and CXCR4 are key determinants of interactions between chronic lymphocytic leukemia (CLL) tumor cells and their microenvironment. In this study, we investigated the effect of CD49d and CXCR4 expressions on survival of CLL cells. Primary CLL cells were cultured with CD49d ligand, VCAM-1, or bone marrow stromal cells (BMSCs); then, apoptosis and immunophenotype analyses were performed. VCAM-1 treatment could not induce direct apoptosis protection or immunophenotype change on the CD49d-expressing CLL cells, but resulted in actin reorganization. The BMSC-induced apoptosis protection was independent from the presence of CD49d expression of CLL cells, but showed an inverse correlation with their CXCR4 expression level. We suppose that CD49d contributes to enhanced survival of leukemic cells by mediating migration to the protective microenvironment, not by direct prevention of apoptosis. Moreover, CLL cells with low CXCR4 expression represent a subpopulation that is more dependent on the microenvironmental stimuli for survival, and show increased "death by neglect" when separated from the supportive niche.
CD49d 和 CXCR4 是慢性淋巴细胞白血病 (CLL) 肿瘤细胞与其微环境相互作用的关键决定因素。在这项研究中，我们研究了 CD49d 和 CXCR4 表达对 CLL 细胞存活的影响。将原代 CLL 细胞与 CD49d 配体 VCAM-1 或骨髓基质细胞 (BMSC) 共培养；然后进行细胞凋亡和免疫表型分析。VCAM-1 处理不能诱导表达 CD49d 的 CLL 细胞直接发生凋亡保护或免疫表型改变，但导致肌动蛋白重组。BMSC 诱导的凋亡保护与 CLL 细胞 CD49d 的表达无关，但与 CXCR4 表达水平呈负相关。我们假设 CD49d 通过介导向保护性微环境的迁移来促进白血病细胞的存活，而不是通过直接防止细胞凋亡。此外，表达低水平 CXCR4 的 CLL 细胞代表一个亚群，对微环境刺激的生存依赖性更强，当从支持龛中分离出来时，更容易出现“被忽视的死亡”。
