Analysis of autoimmune mechanisms of myelodysplastic syndromes

众所周知，许多再生障碍性贫血(AA)患者会发生包括骨髓增生异常综合征(MDS)在内的克隆性疾病。尽管其潜在的机制尚不清楚，但与再生障碍性贫血发病机制有关的细胞毒性T细胞的某种逃逸与MDS的进展有关。在这项研究中，通过对再生障碍性贫血的体细胞突变的综合分析，我们在多达60%的再生障碍性贫血患者中发现了各种基因的频繁体细胞突变。一些突变会影响MDS中的已知突变靶点，如DNMT3A、ASXL1和BCOR。我们的结果可能表明，这些突变靶点可能代表了再生障碍性贫血中CTL的共同靶点，当突变时，这些靶标不仅参与逃避CTL，而且参与MDS的克隆选择。在未来的研究中，应该有理由测试这些突变靶点是否编码由再生障碍性贫血的CTL识别的共同表位。

It was well known that many patients with aplastic anemia (AA) develop clonal disorders including myelodysplastic syndromes (MDS). Although the underlying mechanism is poorly understood, some escape from cytotoxic T-cells involved in AA pathogenesis is implicated in the progression to MDS. In this study, through a comprehensive analysis of somatic mutations in AA, we identified frequent somatic mutations of a wide variety of genes in as many as 60% of patients with AA. Some mutations affected known mutational targets in MDS, such as DNMT3A, ASXL1, and BCOR. Our results may indicated that these mutational targets could represent common targets of CTLs in AA, which when mutated, involved not only in escaping from CTL but also in clonal selection in MDS. It should be warranted in future studies to test whether these mutational targets encode common epitopes that are recognized by CTLs in AA.