Summary
Introduction. Acute myeloid leukemia (AML) and myelodysplastic syndrome (MDS) mostly occur in older people due to somatic mutations. However, in recent years, a hereditary subgroup of these diseases, that is associated with germline mutations has emerged. Most commonly it affects children and young adults. Techno logical advances in gene sequencing over the last decades have made it possible to expand our knowledge of already known hereditary cancer syndromes and to identify new ones, to characterize their specific clinical features, and to identify the pathogenetic mechanisms underlying them. The aim of this article is to review the recent literature on known familial MDS/AML syndromes and the molecular mechanisms involved in the development of the disease.
Methods. The lit er a ture search was per formed us ing OMIM, Orphanet and PubMed da ta bases. Based on the lat est changes to the World Health Organization’s 2016 classification of myeloid neoplasms and acute leukemia, we selected search criteria and analyzed 49 scientific articles published between 2002 and 2020.
Results. The epidemiology of hered i tary MDS/UML, the mode of in heritance, specific clinical features and underlying genetic causes were reviewed. A list of genes associated with MDS/AML was compiled and supplemented with inheritance data.
Conclusions. Although hereditary MDS/AML syn dromes are rare, the young age of the per son with AML, a thor ough collection of family history and, in some cases specific clinical features can help to suspect these diseases. It is important to pay attention to features characteristic of hereditary MDS/AML, as this leads to early diagnosis, which allows the detection of the initial stages of clonal evolution and the use of hematopoietic stem cell trans plan ta tion be fore leukemia develops. The iden ti fi ca tion of he red i tary cancer syndromes and their underlying patho genic variants in genes has implications for decisions on the choice of treat ment for MDS/AML, the use of allogeneic bone marrow transplantation, the genetic screening of related donors for familial mutations, and the assessment of the need for long-term follow-up.
