白血病骨髓微环境研究进展

Advances in understanding leukemia bone marrow microenvironments

骨髓微环境亦称骨髓龛,在造血干细胞维持正常造血功能中发挥关键作用。正常生理条件下,骨髓多种细胞相互调控、共同维持造血稳态;特殊病理情况下,骨髓中的细胞种类、比例、功能发生变化进而促发白血病的发生、发展及耐药。白血病不断恶化不仅由于肿瘤细胞增殖分化异常所致,同时白血病特有的骨髓微环境诱导细胞间黏附,引发细胞因子、趋化因子等分泌异常,促发免疫耐受进而加速疾病进展。本综述重点阐述骨髓微环境中CXC趋化因子配体12/CXC趋化因子受体4等关键促发白血病的信号通路,关注白血病骨髓微环境所致细胞耐药形成机制,展望靶向骨髓微环境治疗白血病、提高患者预后和生存的新策略。

The bone marrow microenvironment,also known as the bone marrow niche,plays a critical role in maintaining the functions of hematopoietic stem cells.Under physiological conditions,various bone marrow cells regulate each other to sustain hematopoietic homeostasis.However,bone marrow cells gain abnormal function under pathological conditions to cause and promote the occurrence of leukemia and induce drug resistance.Recent findings indicate that abnormal proliferation and differentiation are not the sole reason to cause leukemia.Different types of bone marrow cells also induce intercellular adhesion,abnormally secrete cytokines and chemokines,accelerating leukemia's progress.This article reviews the multiple signaling pathways that regulate the formation and progress of leukemia bone marrow niche,such as C-X-C motif chemokine ligand 12/C-X-C motif chemokine receptor 4 signaling pathway,et al.It emphasizes that targeting leukemia bone marrow niche is a vital strategy for improving the leukemia treatment.