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目的 :探讨急性早幼粒细胞白血病(acute promyelocytic leukemia,APL)发病过程中骨髓造血微环境的改变。方法:建立小鼠APL移植模型,联合流式细胞术和体外共培养及集落形成实验对这一模型进行观察,分析APL发病对造血微环境中基质细胞数目和功能的影响,并运用细胞因子检测分析微环境中细胞因子的变化。结果:在APL发病过程中,内皮细胞(endothelial cells,EC)、成骨细胞(osteoblast cells,OBC)等基质细胞的数目明显减少,但间充质干细胞(mesenchymal stem cells,MSC)的数目在早中期基本不受影响,直到疾病晚期才出现降低。与发病小鼠来源的MSC和成骨谱系细胞共培养后,造血干细胞的数目和集落形成数目与对照组相比,均出现减少;另一方面,白血病状态下外周血血清中炎性细胞因子的表达明显增加。结论:APL发病过程中,白血病细胞对于不同类型骨髓基质细胞的增殖具有不同的影响,而白血病状态下的MSC及OBC对造血干细胞的增殖和分化具有抑制作用,这一过程中可能有炎性细胞因子的参与。
Objective: To investigate the change of bone marrow microenvironment in the pathogenesis of acute promyelocytic leukemia (APL). Methods: The mouse APL transplantation model was established. The model was observed by flow cytometry and in vitro co-culture and colony formation assay. The effect of APL on the number and function of stromal cells in hematopoietic microenvironment was analyzed. Cytokines Analyze changes in cytokines in the microenvironment. Results: During the pathogenesis of APL, the number of stromal cells such as endothelial cells (ECs) and osteoblast cells (OBC) decreased significantly, but the number of mesenchymal stem cells The mid-term basically unaffected, until late in the disease appeared to reduce. Compared with the control group, the number of hematopoietic stem cells and the number of colony forming cells co-cultured with the MSC and osteogenic lineage cells of the mice originating from the mice were decreased. On the other hand, the number of inflammatory cytokines The expression increased significantly. CONCLUSIONS: Leukemic cells have different effects on the proliferation of different types of bone marrow stromal cells during the pathogenesis of APL. However, the leukemic MSCs and OBCs can inhibit the proliferation and differentiation of hematopoietic stem cells. In this process, inflammatory cells Factor participation.