急性髓系白血病 (AML) 的种系 (GL) 易感性已在最新的世界卫生组织分类中被确定为独立的疾病实体。根据美国医学遗传学和基因组学学院的指南，如果 GL 变异被归类为“致病性”，则它们被解释为因果关系。 GL易感性可分为具有不同表型的三组，并在成人发病的AML发病机制中发挥重要作用。每个基因的骨髓肿瘤的临床病程和发病年龄差异很大。例如，携带 GATA2 GL 变异的患者会在 30 岁之前患上 AML，并伴有骨髓衰竭，而携带 DDX41 GL 变异的患者往往会在 50 岁之后患上 AML，且之前没有任何血液学异常或器官功能障碍。对移植供体中成人发病的骨髓增生异常综合征的综合分析显示，致病性 GL 变异的频率为 7%，其中 DDX41 是最常见的基因突变，约为 3.8%。未来对任何年龄的髓系肿瘤发病时 GL 易感性的研究将有助于早期准确诊断、制定有效的治疗策略以及选择合适的干细胞移植供体。© 2024。日本血液学会。

Germline (GL) predisposition to acute myeloid leukemia (AML) has been established as an independent disease entity in the latest World Health Organization classification. Following the American College of Medical Genetics and Genomics guidelines, GL variants were interpreted as causal if they were classified as "pathogenic." GL predisposition can be divided into three groups with different phenotypes, and play an important role in the pathogenesis of adult-onset AML. The clinical course and age of onset of myeloid neoplasms varied considerably for each gene. For example, patients with GATA2 GL variants develop AML before the age of 30 along with bone marrow failure, whereas those with DDX41 GL variants tend to develop AML after the age of 50 without any preceding hematological abnormalities or organ dysfunction. A comprehensive analysis of adult-onset myelodysplastic syndromes in transplant donors showed a 7% frequency of pathogenic GL variants, with DDX41 being the most frequent gene mutation at approximately 3.8%. Future research on GL predisposition at any age of myeloid neoplasm onset will assist in early and accurate diagnosis, development of effective treatment strategies, and selection of suitable donors for stem cell transplantation.© 2024. Japanese Society of Hematology.