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目的:应用急性早幼粒细胞白血病(APL)小鼠模型研究白血病发病过程中白血病细胞和正常造血细胞增殖、定位和迁移的特点。方法:采用小鼠白血病移植实验及流式细胞术,监测其白血病发病过程中,骨髓和脾脏中白血病细胞和正常长期造血干细胞、免疫细胞组分的动态变化。结果:在APL模型小鼠的白血病发病过程中,骨髓中正常粒单系造血祖细胞在发病晚期呈现下降趋势,正常长期造血干细胞和共同淋巴祖细胞在发病晚期也明显下降。与之相反,在白血病发病过程中,脾脏正常长期造血干细胞未见明显下降,并呈现定位迁移或代偿增生的趋势,发病晚期,正常长期造血干细胞、共同淋巴祖细胞数量均显著上升。结论:白血病发病过程中正常长期造血干细胞和祖细胞及免疫细胞在细胞数量和造血器官的定位发生显著变化,提示造血微环境可能参与白血病的发生和发展过程。
Objective: To study the characteristics of proliferation, localization and migration of leukemia cells and normal hematopoietic cells in the pathogenesis of leukemia using acute promyelocytic leukemia (APL) mouse model. Methods: Mouse leukemia transplantation experiment and flow cytometry were used to monitor the dynamic changes of leukemia cells and normal long-term hematopoietic stem cells and immune cells in the bone marrow and spleen of leukemia patients. Results: In the pathogenesis of leukemia in APL model mice, the normal mononuclear hematopoietic progenitor cells in the bone marrow showed a declining trend in the late stage of onset, and the normal long-term hematopoietic stem cells and common lymphoid progenitor cells also significantly decreased in the late onset stage. On the contrary, in the process of leukemia, the long-term normal hematopoietic stem cells of the spleens showed no obvious decline, and showed the tendency of migration or compensatory proliferation. In the late onset, the number of normal long-term hematopoietic stem cells and common lymphoid progenitor cells increased significantly. Conclusion: The normal long-term hematopoietic stem cells, progenitor cells and immune cells in the process of leukemia have significant changes in the number of cells and the location of hematopoietic organs, suggesting that hematopoietic microenvironment may be involved in the occurrence and development of leukemia.