Department of Genetics, the University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.
Int J Cancer. 2013 Aug 1;133(3):525-33. doi: 10.1002/ijc.27896. Epub 2012 Oct 29.
Myelodysplastic syndromes (MDSs) are clonal hematopoietic stem cell (HSC) malignancies that are characterized by ineffective hematopoiesis and frequent progression to acute myeloid leukemia (AML). Thus far, few treatments can actually alter the natural history of this disease. Allogeneic stem-cell transplantation for high-risk MDS is becoming the only curative therapy probably because of the improvement of bone marrow transplant procedures. The lack of other options underscores the urgent need to develop new therapy. The prevailing model suggests that genetic and/or epigenetic alterations that occur in HSCs or HSC niche compromise HSC function, resulting in MDS; therefore, MDS HSCs are likely the ideal targets for MDS treatment. Recent encouraging advances--capturing a molecular portrait of the whole genome of MDS CD34(+) cells, including identifying altered signaling pathways and altered microRNAs--have improved our understanding of MDS pathogenesis and provided novel potential clinical targets for MDS. Here, I will briefly review the characteristics of MDS HSCs and discuss the therapeutic promise of targeting MDS HSCs.
骨髓增生异常综合征（MDS）是一种克隆性造血干细胞（HSC）恶性肿瘤，其特征为无效造血和频繁向急性髓系白血病（AML）进展。到目前为止，很少有治疗方法可以真正改变这种疾病的自然病程。高危 MDS 的异基因造血干细胞移植正在成为唯一可能的治愈性治疗方法，可能是因为骨髓移植程序的改进。缺乏其他选择突出表明迫切需要开发新的治疗方法。目前流行的模型表明，发生在 HSCs 或 HSC 龛中的遗传和/或表观遗传改变会损害 HSC 功能，导致 MDS；因此，MDS HSCs 可能是 MDS 治疗的理想靶点。最近令人鼓舞的进展——捕捉 MDS CD34(+)细胞全基因组的分子特征，包括鉴定改变的信号通路和改变的 microRNAs——提高了我们对 MDS 发病机制的理解，并为 MDS 提供了新的潜在临床靶点。在这里，我将简要回顾 MDS HSCs 的特征，并讨论针对 MDS HSCs 的治疗前景。
