title: Analysis of GATA1 mutations in Down syndrome transient myeloproliferative disorder and myeloid leukemia.
abstract: Children with Down syndrome (DS) up to the age of 4 years are at a 150-fold excess risk of developing myeloid leukemia (ML-DS). Approximately 4%-5% of newborns with DS develop transient myeloproliferative disorder (TMD). Blast cell structure and immunophenotype are similar in TMD and ML-DS. A mutation in the hematopoietic transcription factor GATA1 is present in almost all cases. Here, we show that simple techniques detect GATA1 mutations in the largest series of TMD (n = 134; 88%) and ML-DS (n = 103; 85%) cases tested. Furthermore, no significant difference in the mutational spectrum between the 2 disorders was seen. Thus, the type of GATA1 sequence mutation is not a reliable tool and is not prognostic of which patients with TMD are probable to develop ML-DS.
authors.affiliation: Molecular Haematology Unit, Weatherall Institute of Molecular Medicine, University of Oxford, John Radcliffe Hospital, Oxford, UK.
authors.forename: Kate A
authors.initials: KA
authors.lastname: Alford
authors.forename: Katarina
authors.initials: K
authors.lastname: Reinhardt
authors.forename: Catherine
authors.initials: C
authors.lastname: Garnett
authors.forename: Alice
authors.initials: A
authors.lastname: Norton
authors.forename: Katarina
authors.initials: K
authors.lastname: Böhmer
authors.forename: Christine
authors.initials: C
authors.lastname: von Neuhoff
authors.forename: Alexandra
authors.initials: A
authors.lastname: Kolenova
authors.forename: Emanuele
authors.initials: E
authors.lastname: Marchi
authors.forename: Jan-Henning
authors.initials: JH
authors.lastname: Klusmann
authors.forename: Irene
authors.initials: I
authors.lastname: Roberts
authors.forename: Henrik
authors.initials: H
authors.lastname: Hasle
authors.forename: Dirk
authors.initials: D
authors.lastname: Reinhardt
authors.forename: Paresh
authors.initials: P
authors.lastname: Vyas
mesh_terms: D002675:Child, Preschool; D004252:DNA Mutational Analysis; D004314:Down Syndrome / Q000150:complications* / Q000235:genetics*; D005260:Female; D050982:GATA1 Transcription Factor / Q000235:genetics*; D005820:Genetic Testing; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D007951:Leukemia, Myeloid / Q000150:complications* / Q000235:genetics*; D008297:Male; D009154:Mutation; D009196:Myeloproliferative Disorders / Q000150:complications* / Q000235:genetics*; D011379:Prognosis
chemical_list: D050982:GATA1 Transcription Factor; C494688:GATA1 protein, human