Myeloid neoplasms with and without preexisting platelet disorders frequently develop in association with an underlying germline predisposition. Germline alterations affecting ANKRD26, CEBPA, DDX41, ETV6, and RUNX1 are associated with nonsyndromic predisposition to the development of myeloid neoplasms including acute myeloid leukemia and myelodysplastic syndrome. However, germline predisposition to myeloid neoplasms is also associated with a wide range of other syndromes, including SAMD9/9L associated predisposition, GATA2 deficiency, RASopathies, ribosomopathies, telomere biology disorders, Fanconi anemia, severe congenital neutropenia, Down syndrome, and others. In the fifth edition of the World Health Organization (WHO) series on the classification of tumors of hematopoietic and lymphoid tissues, myeloid neoplasms associated with germline predisposition have been recognized as a separate entity. Here, we review several disorders from this WHO entity as well as other related conditions with an emphasis on the molecular pathogenesis of disease and accompanying somatic alterations. Finally, we provide an overview of establishing the molecular diagnosis of these germline genetic conditions and general recommendations for screening and management of the associated hematologic conditions.

中文翻译：

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髓系肿瘤的遗传易感性：发病机制和临床意义


伴有或不伴有先前存在的血小板疾病的髓系肿瘤经常与潜在的种系易感性有关。影响 ANKRD26、 CEBPA 、 DDX41 、 ETV6 和 RUNX1 的种系改变与髓系肿瘤发展的非综合征易感性有关，包括急性髓系白血病和骨髓增生异常综合征。然而，髓系肿瘤的种系易感性也与广泛的其他综合征有关，包括 SAMD9/9L 相关易感性、GATA2 缺陷、RASopathies、核糖体病、端粒生物学疾病、Fanconi 贫血、严重的先天性中性粒细胞减少症、唐氏综合征等。在世界卫生组织 （WHO） 关于造血和淋巴组织肿瘤分类的系列文章的第五版中，与种系易感性相关的髓系肿瘤已被认定为一个单独的实体。在这里，我们回顾了来自该 WHO 实体的几种疾病以及其他相关疾病，重点是疾病的分子发病机制和伴随的躯体改变。最后，我们概述了建立这些种系遗传病的分子诊断，以及筛查和管理相关血液病的一般建议。