Department of Hematology, Erasmus MC Cancer Institute, Rotterdam, The Netherlands.
Blood. 2019 Mar 7;133(10):1031-1038. doi: 10.1182/blood-2018-10-844639. Epub 2019 Jan 22.
Myelodysplastic syndrome (MDS) is characterized by bone marrow failure and a strong propensity for leukemic evolution. Somatic mutations are critical early drivers of the disorder, but the factors enabling the emergence, selection, and subsequent leukemic evolution of these "leukemia-poised" clones remain incompletely understood. Emerging data point at the mesenchymal niche as a critical contributor to disease initiation and evolution. Disrupted inflammatory signaling from niche cells may facilitate the occurrence of somatic mutations, their selection, and subsequent clonal expansion. This review summarizes the current concepts about "niche-facilitated" bone marrow failure and leukemic evolution, their underlying molecular mechanisms, and clinical implications for future innovative therapeutic targeting of the niche in MDS.
骨髓增生异常综合征（MDS）的特征是骨髓衰竭和强烈的白血病演变倾向。体细胞突变是该疾病的关键早期驱动因素，但使这些“白血病倾向”克隆出现、选择和随后白血病演变的因素仍不完全清楚。新出现的数据表明间质龛是疾病发生和演变的关键贡献者。龛细胞中失调的炎症信号可能促进体细胞突变的发生、选择和随后的克隆扩增。这篇综述总结了目前关于“龛辅助”骨髓衰竭和白血病演变的概念，及其潜在的分子机制，以及对 MDS 中龛的未来创新治疗靶向的临床意义。
