title: Familial Acute Myeloid Leukemia and Myelodysplasia in Hungary.
abstract: Although genetic predisposition to haematological malignancies has long been known, genetic testing is not yet the part of the routine diagnostics. In the last ten years, next generation sequencing based studies identified novel germline mutations in the background of familial aggregation of certain haematologic disorders including myelodysplastic syndromes (MDS) and acute myeloid leukaemia (AML). This is supported by the fact that the myeloid neoplasms with genetic predisposition represent a new category in the revised 2016 World Health Organization classification. According to the new classification, these disorders are subdivided based on the clinical and genetic features, including myeloid neoplasms with germline predisposition alone, or with pre-existing platelet disorder, cytopaenias or other organ failures. The predisposing genetic factors include mutations in the RUNX1, CEBPA, GATA2, ANKRD26, ETV6, DDX41, TERC or TERT and SRP72 genes. The genes affected in these syndromes are important regulators of haemopoiesis and are frequently implicated in leukaemogenesis, providing deeper insight into the understanding of normal and malignant haemopoiesis. Despite the growing knowledge of germline predisposing events in the background of familial myeloid malignancies, the germline genetic component is still unknown in a subset of these pedigrees. Here, we present the first study of inherited myeloid malignancies in Hungary. We identified three families with apparent clustering of myeloid malignancies with nine affected individuals across these pedigrees. All tested individuals were negative for CEBPA, GATA2, RUNX1, ANKRD26, ETV6, DDX41, TERC or TERT and SRP72 mutations, suggesting the presence of so far unidentified predisposing mutations.
authors.affiliation: MTA-SE Lendület Molecular Oncohematology Research Group, 1st Department of Pathology and Experimental Cancer Research, Semmelweis University, Budapest, Hungary.
authors.forename: Attila Péter
authors.initials: AP
authors.lastname: Király
authors.affiliation: Pediatric Hematology and Stem Cell Transplantation Unit, United St. István and St. László Hospital, Budapest, Hungary.
authors.forename: Krisztián
authors.initials: K
authors.lastname: Kállay
authors.affiliation: MTA-SE Lendület Molecular Oncohematology Research Group, 1st Department of Pathology and Experimental Cancer Research, Semmelweis University, Budapest, Hungary.
authors.forename: Ambrus
authors.initials: A
authors.lastname: Gángó
authors.affiliation: Department of Hematology, Kaposi Mor Teaching Hospital, Kaposvár, Hungary.
authors.forename: Ádám
authors.initials: Á
authors.lastname: Kellner
authors.affiliation: Department of Hematology, Kaposi Mor Teaching Hospital, Kaposvár, Hungary.
authors.forename: Miklós
authors.initials: M
authors.lastname: Egyed
authors.affiliation: 2nd Department of Medicine and Cardiology Centre, Medical Faculty, Albert Szent-Györgyi Clinical Centre, University of Szeged, Szeged, Hungary.
authors.forename: Anita
authors.initials: A
authors.lastname: Szőke
authors.affiliation: MTA-SE Lendület Molecular Oncohematology Research Group, 1st Department of Pathology and Experimental Cancer Research, Semmelweis University, Budapest, Hungary.
authors.forename: Richárd
authors.initials: R
authors.lastname: Kiss
authors.affiliation: United St. István and St. László Hospital, Budapest, Hungary.
authors.forename: István
authors.initials: I
authors.lastname: Vályi-Nagy
authors.affiliation: MTA-SE Lendület Molecular Oncohematology Research Group, 1st Department of Pathology and Experimental Cancer Research, Semmelweis University, Budapest, Hungary.
authors.forename: Judit
authors.initials: J
authors.lastname: Csomor
authors.affiliation: MTA-SE Lendület Molecular Oncohematology Research Group, 1st Department of Pathology and Experimental Cancer Research, Semmelweis University, Budapest, Hungary.
authors.forename: András
authors.initials: A
authors.lastname: Matolcsy
authors.affiliation: MTA-SE Lendület Molecular Oncohematology Research Group, 1st Department of Pathology and Experimental Cancer Research, Semmelweis University, Budapest, Hungary. bodor.csaba1@med.semmelweis-univ.hu.
authors.forename: Csaba
authors.identifier: http://orcid.org/0000-0002-0729-692X
authors.initials: C
authors.lastname: Bödör
mesh_terms: D000293:Adolescent; D000328:Adult; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000235:genetics*; D002648:Child; D005260:Female; D005500:Follow-Up Studies; D020022:Genetic Predisposition to Disease; D005820:Genetic Testing; D006801:Humans; D006814:Hungary / Q000453:epidemiology; D015470:Leukemia, Myeloid, Acute / Q000453:epidemiology / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D009154:Mutation; D009190:Myelodysplastic Syndromes / Q000453:epidemiology / Q000235:genetics*; D010375:Pedigree; D011379:Prognosis; D055815:Young Adult
chemical_list: D014408:Biomarkers, Tumor
keywords: Familial MDS/AML; Genetic predisposition; Germline mutation