再生障碍性贫血和克隆演变：种系和体细胞遗传学

Aplastic anemia and clonal evolution：germline and somatic genetics

对于骨髓衰竭（BMF）的患者,克隆演变为骨髓增生异常综合征（MDS）或急性髓系白血病（AML）仍然是一个严重的并发症.明确演变为MDS或者AML的危险因素可以为个体化治疗方案提供信息,并确定早期或前期进行造血干细胞移植可能受益的患者.目前,临床实验室可以进行二代DNA测序,研究集中在种系和体细胞突变对BMF患者诊断和监测的应用.大多数种系遗传性BMF疾病具有高倾向MDS或AML转化的特征.近来BMF的体细胞突变研究发现高频的克隆性造血干细胞具有获得性基因突变,这些基因与MDS或AML相关.文章就第58届美国血液学会（ASH）年会中对于BMF患者进展为克隆性疾病的种系和体细胞突变的评价以及临床基因检测的挑战进行介绍.

Clonal progression to myelodysplastic syndromes （MDS） or acute myeloid leukemia （AML） remains a dreaded complication for a subset of patients with bone marrow failure （BMF）. Recognizing risk factors for the development of MDS or AML would inform individualized treatment decisions and identify patients who may benefit from early or upfront hematopoietic stem cell transplantation. Now that next-generation DNA sequencing is available in the clinical laboratory, research has focused on the implications of germline and somatic mutations for diagnosing and monitoring patients with BMF. Most germline genetic BMF disorders are characterized by a high propensity to develop MDS or AML. Recent studies of somatic variants in marrow failure revealed a high frequency of clonal hematopoiesis with the acquisition of mutations in genes associated with MDS or AML. The evaluation and implications of germline and somatic mutations for the development of clonal disorders in patients with BMF and challenges of clinical genetic testing will be summarized in this paper based on the reports from the 58th American Society of Hematology （ASH） Annual Meeting.