Oh Il-Hoan, Jeong Seon-Yeong, Kim Jin-A
Catholic High-Performance Cell Therapy Center.
Department of Medical Lifescience, The Catholic University of Korea, College of Medicine, Seoul, Korea.
Curr Opin Hematol. 2019 Jul;26(4):249-257. doi: 10.1097/MOH.0000000000000508.
Normal hematopoietic stem cells (HSCs) and leukemic stem cells (LSCs) interact with the stem cell niche bone marrow in different ways. Understanding the potentially unique microenvironmental regulation of LSCs is key to understanding in-vivo leukemogenic mechanisms and developing novel antileukemic therapies.
When leukemic cells are engrafted in the stem cell niche, the cellular nature of the niche - including mesenchymal stromal cells - is reprogramed. Altered mesenchymal cells selectively support leukemic cells and reinforce the pro-leukemic environment. As the niche plays an active role in leukemogenesis, its remodeling may significantly influence the leukemogenic pattern, and cause differences in clinical prognosis. Notably, niche cells could be stimulated to revert to a pronormal/antileukemic state, creating potential for niche-based antileukemic therapy.
Bone marrow microenvironments are under dynamic regulation for normal and leukemic cells, and there is bi-directional control of leukemic cells in the niche. Leukemic cells are both protected by stroma and able to reprogram stromal cells to transform the niche to a state, which reinforces leukemogenesis. Because of its dynamic nature, the niche could be converted to an environment with antileukemic properties, making it an attractive target for therapy.
正常造血干细胞（HSCs）和白血病干细胞（LSCs）与干细胞微环境骨髓以不同方式相互作用。了解LSCs潜在独特的微环境调节是理解体内白血病发生机制和开发新型抗白血病疗法的关键。
当白血病细胞植入干细胞微环境时，微环境的细胞性质——包括间充质基质细胞——会被重新编程。改变的间充质细胞选择性地支持白血病细胞并强化促白血病环境。由于微环境在白血病发生中起积极作用，其重塑可能显著影响白血病发生模式，并导致临床预后差异。值得注意的是，微环境细胞可被刺激恢复到促正常/抗白血病状态，为基于微环境的抗白血病治疗创造了潜力。
骨髓微环境对正常细胞和白血病细胞处于动态调节中，微环境中对白血病细胞存在双向控制。白血病细胞既受到基质保护，又能够重新编程基质细胞，将微环境转变为一种强化白血病发生的状态。由于其动态性质，微环境可转变为具有抗白血病特性的环境，使其成为有吸引力的治疗靶点。
