Division of Hematology, Department of Medicine, QEII Health Sciences Centre, Dalhousie University, Halifax, NS, Canada.
Department of Internal Medicine, Section of Hematology, Oncology and Rheumatology, Heidelberg University Hospital, Heidelberg, Germany.
Best Pract Res Clin Haematol. 2024 Mar;37(1):101537. doi: 10.1016/j.beha.2024.101537. Epub 2024 Feb 1.
Myeloid neoplasms with germline predisposition have been recognized increasingly over the past decade with numerous newly described disorders. Penetrance, age of onset, phenotypic heterogeneity, and somatic driver events differ widely among these conditions and sometimes even within family members with the same variant, making risk assessment and counseling of these individuals inherently difficult. In this review, we will shed light on high malignant penetrance (e.g., CEBPA, GATA2, SAMD9/SAMD9L, and TP53) versus variable malignant penetrance syndromes (e.g., ANKRD26, DDX41, ETV6, RUNX1, and various bone marrow failure syndromes) and their clinical features, such as variant type and location, course of disease, and prognostic markers. We further discuss the recommended management of these syndromes based on penetrance with an emphasis on somatic aberrations consistent with disease progression/transformation and suggested timing of allogeneic hematopoietic stem cell transplant. This review will thereby provide important data that can help to individualize and improve the management for these patients.
在过去的十年中，随着越来越多的新描述的疾病的出现，人们已经越来越认识到具有种系易感性的骨髓增生性肿瘤。这些疾病之间的外显率、发病年龄、表型异质性和体细胞驱动事件差异很大，有时甚至在具有相同变异的家庭成员之间也存在差异，这使得对这些个体进行风险评估和咨询具有固有的难度。在这篇综述中，我们将重点介绍高恶性外显率（例如 CEBPA、GATA2、SAMD9/SAMD9L 和 TP53）与恶性外显率可变的综合征（例如 ANKRD26、DDX41、ETV6、RUNX1 和各种骨髓衰竭综合征）及其临床特征，例如变异类型和位置、病程和预后标志物。我们进一步讨论了基于外显率的这些综合征的推荐管理，重点是与疾病进展/转化一致的体细胞异常以及同种异体造血干细胞移植的建议时间。这篇综述将提供重要的数据，有助于为这些患者进行个体化和改进管理。
