Department of Internal Medicine V, Hematology, Oncology and Rheumatology, Heidelberg University Hospital and Clinical Cooperation Unit Molecular Hematology/Oncology, German Cancer Research Center (DKFZ) Heidelberg, Germany; Department of Internal Medicine V, Hematology, Oncology and Rheumatology, Heidelberg University Hospital, Heidelberg, Germany; Medical Oncology, National Center for Tumor Diseases (NCT), Heidelberg University Hospital, Heidelberg, Germany; Section Head of Translational Gynecology, University Women's Hospital Heidelberg, German Cancer Consortium (DKTK), Heidelberg, Germany; Institute of Pathology, Department of Applied Tumor Biology, Heidelberg University Hospital, Heidelberg, Germany.
Dtsch Arztebl Int. 2018 Dec 14;115(50):848-854. doi: 10.3238/arztebl.2018.0848.
Some hematological malignancies arise in persons with a hereditary predisposition. The hereditary nature of these diseases often goes unrecognized, particularly when symptoms begin in adulthood.
This review is based on pertinent publications retrieved by a selective search in PubMed.
Many rare germline mutations have been identified that lead to acute leukemia and myelodysplastic syndromes. They differ from one another with respect to their penetrance, the age of onset of disease, and the clinical manifestations. In view of this heterogeneity, no uniform recommendations have yet been formulated for their diagnosis and treatment. The most common types of hematological malig- nancy with a hereditary predisposition are traceable to an underlying disturbance of DNA damage response and repair mechanisms and to mutations of hematological transcription factors. With regard to the selection of patients for testing, the con- sensus is that cytogenetic and molecular-genetic findings that are suspect for a hereditary predisposition, such as CEBPA and RUNX1 mutations, call for further investigation, as do any clinical features that are typical of tumor syndromes, or a positive family history. The knowledge that a hereditary predisposition may be present is highly stressful for patients; testing should only be carried out after the patient has received genetic counseling. The confirmation of a germline mutation always requires a comparison with healthy tissue. A fibroblast culture is recom- mended as the gold standard for this purpose.
The detection of a hereditary predisposition to hematological neoplasia is often relevant to treatment and follow-up care: for example, it may motivate early allogeneic stem-cell transplantation. Counseling, predictive testing, and follow-up care are available to the patients' relatives as well.
一些血液系统恶性肿瘤发生在具有遗传易感性的个体中。这些疾病的遗传性通常未被识别，尤其是当症状在成年后开始出现时。
本综述基于在 PubMed 中进行选择性搜索所检索到的相关出版物。
已经鉴定出许多导致急性白血病和骨髓增生异常综合征的罕见种系突变。它们在外显率、疾病发病年龄和临床表现方面存在差异。鉴于这种异质性，尚未针对其诊断和治疗制定统一的建议。具有遗传易感性的最常见类型的血液系统恶性肿瘤可归因于 DNA 损伤反应和修复机制的潜在紊乱以及血液系统转录因子的突变。关于对患者进行检测的选择，共识是，对于疑似遗传易感性的细胞遗传学和分子遗传学发现，如 CEBPA 和 RUNX1 突变，需要进一步调查，任何典型的肿瘤综合征的临床特征或阳性家族史也是如此。存在遗传易感性的可能性对患者来说压力很大；只有在患者接受遗传咨询后，才能进行检测。种系突变的确认始终需要与健康组织进行比较。为此目的，建议使用成纤维细胞培养作为金标准。
检测血液系统肿瘤的遗传易感性通常与治疗和随访护理相关：例如，它可能促使早期异基因干细胞移植。咨询、预测测试和随访护理也可提供给患者的亲属。
