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.

Clinical features ofDDX41mutation-related diseases: a systematic review with individual patient data

“…We excluded 77 publications, including 41 animal studies, 20 about irrelevant subjects, 13 reviews, and three in languages other than English and Chinese. The remaining 30 were next given full-text reviews and all were considered eligible for this study, including nine case series, 12 , 14 – 21 11 case reports, 22 – 32 four reports about DDX41 -related solid cancers, 33 – 36 and six rare case reports 37 – 42 ( Figure 1 ). No extra study was identified from the references listed in the relevant reviews and the included studies.…”

“…DDX41 mutation was negatively detected in Hungary. 40 One hundred and thirty-five patients had both germline and somatic DDX41 mutations.…”

CEBPA-mutációk vizsgálata és prognosztikai jelentőségük akut myeloid leukémiában

“…A familiáris MDS/AML kialakulásának hátterében számos autoszomális domináns módon öröklődő mutációk állnak, melyek alapján négy szindrómát különítünk meg: 1) a CEBPA-pozitív familiáris MDS/AML-t, 2) a GATA2-pozitív familiáris MDS/AML-t, 3) a familiáris vérlemezke-funkciózavar kapcsán kialakuló MDS/AML-t RUNX1-pozitivitással, és 4) a csontvelő-kimerüléssel járó kórképek TERT és TERC génmutációval, illetve egyéb gének, mint a ANKRD26, ETV6, DDX41, SRP72 stb.) eltéréseivel [29,30]. A fentiek tükrében bizonyos életkor alatt (pl.…”

“…A fentiek tükrében bizonyos életkor alatt (pl. 40 év) érdemes lenne a CEBPA-mutáció csíravonalbeli eredetét tesztelni, mivel ezen öröklődő mutációkat hordozó esetek nagy részét hazánkban még nem ismerjük, a genetikai eltérések időbeni felismerése pedig biztosíthatja a vizsgált személy megfelelő nyomon követését, a csontvelő-transzplantáció egyéni elbírálását és a tünetmentes vérrokonok kiszűrését [29,30]. Amennyiben a CEBPA-mutáció örökletesnek bizonyul, a beteg testvére nem lehet donor.…”

A case diagnosis as acute myeloid leukemia on a Family Medicine Policlinic

“…Trombositopeninin en önemli nedenleri; kemik iliğinde yetersiz üretim ve trombosit ömrünün kısalmasıdır. (5) Düşük sayıda granül içeren, dev boyutta, fonksiyon bozukluğu gösteren trombositlere rastlanabilir. (6) Periferik kanda, ciddi lökopenisi olan hastalar dışında miyeloblastların görülmesi beklenir.…”