Abstract:
BACKGROUND: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. METHODS:This review is based on pertinent publications retrieved by a selective search in PubMed. RESULTS: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. CONCLUSION: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.
journal_name
Dtsch Arztebl Intjournal_title
Deutsches Arzteblatt internationalauthors
Bochtler T,Haag GM,Schott S,Kloor M,Krämer A,Müller-Tidow Cdoi
10.3238/arztebl.2018.0848subject
Has Abstractpub_date
2018-12-14 00:00:00pages
848-854issue
50issn
1866-0452pii
arztebl.2018.0848journal_volume
115pub_type
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