Pang Yan-Bin, Li Wen-Wen, Luo Jian-Min, Ji Jing, DU Xin
Department of Hematology, The Afilliatied Hospital of Hebei Universtity, Baoding 071000, Hebei Province, China.
Department of Hematology, The Second Hospital of Hebei Medical University, Shijiazhuang 050000, Hebei Province, China.
Zhongguo Shi Yan Xue Ye Xue Za Zhi. 2018 Jun;26(3):942-946. doi: 10.7534/j.issn.1009-2137.2018.03.053.
Myelodysplastic syndromes (MDS) comprise a group of malignant hematopoietic stem cell (HSC) disorders characterized by ineffective hematopoiesis. The risk of transformation to acute myeloid leukemia (AML) is increasing. The initiating event in HSC of MDS leads to a growth advantage and subsequent clonal expansion, that is still poorly understood. Accumulating data indicate that the mesenchymal stem cells(MSCs) in MDS model display aberrant characteristics contributing to disease initiation and transformation into AML. MSC derived from MDS displayed the alteration in genetics, epigenetics and gene expression, which contribute to altered morphology, impaired proliferative and differentiation capacity and perturbed cytokine secretions, thus destroy in their ability to support normal hematopoiesis and contribute to malignant progression. A number of promising agents that target the interactions of the MDS clone with MSC are currently investigated in various phases of clinical trial, that might ultimately result in novel therapeutic strategies, targeting niche cells to attenuate leukemic progression. In this article, the current status of MDS treatment, the characteristics of MDS-MSC senescence and phenotypes, the changes of hematopoietic function sapported by senescent MDS-MSC, the significane of MDS-MSC in MDS prognosis and the MDS-MSC as potential target for treatment of MDS are summarized.
骨髓增生异常综合征(MDS)是一组以无效造血为特征的恶性造血干细胞(HSC)疾病。转化为急性髓系白血病(AML)的风险正在增加。MDS造血干细胞中的起始事件导致生长优势和随后的克隆性扩增,对此仍知之甚少。越来越多的数据表明,MDS模型中的间充质干细胞(MSC)表现出异常特征,有助于疾病的起始和向AML的转化。源自MDS的MSC在遗传学、表观遗传学和基因表达方面发生改变,这导致形态改变、增殖和分化能力受损以及细胞因子分泌紊乱,从而破坏其支持正常造血的能力并促进恶性进展。目前,一些针对MDS克隆与MSC相互作用的有前景的药物正在临床试验的各个阶段进行研究,这最终可能会产生新的治疗策略,即靶向微环境细胞以减轻白血病进展。本文总结了MDS治疗的现状、MDS-MSC衰老和表型的特征、衰老的MDS-MSC支持的造血功能变化、MDS-MSC在MDS预后中的意义以及MDS-MSC作为MDS治疗潜在靶点的情况。