急性早幼粒细胞白血病小鼠模型中造血增殖、定位和迁移特点的研究

Study on hematopoietic cell proliferation,localization and migration in development of acute promyelocytic leukemia in mice model

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 investigate the characteristics of proliferation, localization and migration of leukemic and normal hematopoietic cells in the development of leukemia in acute promyelocytic leukemia mice model. Methods Mice leukemia transplantation and flow cytometry were used to monitor the dynamic changes of bone marrow and splenic leukemic ceils and normal hematopoietic cells in the development of leukemia in mice. Results In acute promyelocytic leukemia mice model, bone marrow normal granulo-monocytic progenitors, and normal hematopoietic stem cells and common lymphoid precursors were significantly reduced in the final stage of leukemia during the development of leukemia. In contrast, spleen hematopoiesis was not decreased and showed a trend of localization migration and compensatory proliferation, and normal hematopoietic stem ceils and common lymphoid precursor cells were significantly increased in the late stage. Conclusions Normal hematopoietic stem/progenitor cells and immune cells showe significant change in volume and hematopoietic organ localization during the development of leukemia, suggesting hematopoietic microenvironment might be involved in the development and progress of leukemia.