Department of Cancer Genetics with Cytogenetic Laboratory, Medical University of Lublin, Lublin, Poland.
Chair and Department of Neurology, Medical University of Lublin, Lublin, Poland.
Acta Haematol. 2023;146(4):277-286. doi: 10.1159/000526397. Epub 2023 Apr 4.
Both microenvironmental signals from surrounding cells and changes in the genome of leukemic cells play essential role in the development of chronic lymphocytic leukemia. Nurse-like cells (NLCs) are one of the important elements of the microenvironment of CLL cells. The key role in the interactions of leukemic cells with NLCs is played by chemokines, which may interfere with the programmed cell death process in the leukemic lymphocytes. The aim of our study was analysis of selected microenvironmental factors having a potential impact on the leukemic cells survival, as well as their association with clinical, cytogenetic, and molecular parameters. For this study, we selected three types of molecules which can modulate microenvironment: chemokines IL-8 and CCL3 (which are classically secreted to extracellular matrix), soluble forms of adhesion molecules JAG1 and CD163, and secreted form of endogenous protein BIRC5. We assessed their expression in the serum of CLL patients as well as in medium of long-term NLCs cultures.
Long-term cell culture was prepared from mononuclear cells derived from the blood of 34 patients with CLL. Number of NLCs cells was evaluated, under a light inverted microscope. The concentration of IL-8, CCL3, sBIRC5, sCD163, and sJAG1 in culture medium and serum was assessed by enzyme-linked immunosorbent assays.
There were significant differences in the concentration of IL-8, sBIRC5, CCL3, sCD163, and sJAG1 between the patient's blood serum and the culture medium. The concentrations of IL-8, CCL3, and JAG1 were higher in the culture medium, which confirmed the role of the microenvironment in the production of these proteins. In addition, the concentration of CCL3 chemokine in both patient's blood serum and in the culture medium correlated with the number of NLCs and with known prognostic factors in the course of CLL, e.g., Rai stage, WBC, expression of ZAP-70, CD38, and CD5/19.
The microenvironment of CLL cells, which includes NLCs, plays an important role in the pathogenesis of CLL. The CCL3 chemokine seems to be a good factor representing microenvironment of CLL cells. Chronic lymphocytic leukemia is a complex and very heterogeneous disease; therefore, its progress should be considered both in the context of genetic changes and the interaction with microenvironmental cells.
周围细胞的微环境信号和白血病细胞基因组的变化在慢性淋巴细胞白血病的发展中都起着至关重要的作用。类滋养细胞（NLCs）是 CLL 细胞微环境的重要组成部分之一。趋化因子在白血病细胞与 NLCs 的相互作用中起着关键作用，它们可能会干扰白血病淋巴细胞的程序性细胞死亡过程。我们研究的目的是分析对白血病细胞存活有潜在影响的选定微环境因素，并分析它们与临床、细胞遗传学和分子参数的关系。为此，我们选择了三种可调节微环境的分子类型：趋化因子 IL-8 和 CCL3（经典分泌到细胞外基质）、黏附分子可溶性形式 JAG1 和 CD163，以及内源性蛋白 BIRC5 的分泌形式。我们评估了它们在 CLL 患者血清和长期 NLCs 培养物中的表达。
从 34 例 CLL 患者的血液中分离出单核细胞，制备长期细胞培养物。在倒置显微镜下评估 NLCs 细胞的数量。通过酶联免疫吸附试验评估培养基和血清中 IL-8、CCL3、sBIRC5、sCD163 和 sJAG1 的浓度。
患者血清和培养基之间的 IL-8、sBIRC5、CCL3、sCD163 和 sJAG1 浓度存在显著差异。培养基中 IL-8、CCL3 和 JAG1 的浓度较高，这证实了微环境在这些蛋白产生中的作用。此外，CCL3 趋化因子在患者血清和培养基中的浓度与 NLCs 的数量以及 CLL 病程中的已知预后因素相关，例如 Rai 分期、WBC、ZAP-70、CD38 和 CD5/19 的表达。
包括 NLCs 在内的 CLL 细胞的微环境在 CLL 的发病机制中起着重要作用。趋化因子 CCL3 似乎是代表 CLL 细胞微环境的一个很好的因素。慢性淋巴细胞白血病是一种复杂且非常异质的疾病；因此，应考虑到遗传变化及其与微环境细胞的相互作用，来考虑其进展。
