title: GATA1 mutation and trisomy 21 are required only in haematopoietic cells for development of transient myeloproliferative disorder.
abstract: Trisomy 21 [Down's syndrome (DS)] and mutations in transcription factor GATA1 predispose neonates to a transient myeloproliferative disorder (TMD) and/or acute megakaryocytic leukaemia (AMKL). The role of trisomy 21 in their pathogenesis is unclear. We previously reported two rare neonates without DS who had TMD, one of whom progressed to AMKL. Trisomy 21 was detected only in blood cells at presentation with TMD/AMKL and disappeared with disease resolution. We now show that the blood cells at presentation of TMD harboured GATA1 genomic DNA mutations, suggesting a requirement for trisomy 21 in haematopoietic cells, rather than other cell types, for development of TMD/AMKL.
authors.affiliation: Department of Haematology and MRC Molecular Haematology Unit, Weatherall Institute of Molecular Medicine, Oxford Radcliffe Hospital, Oxford OX3 9DU, UK.
authors.forename: Emily
authors.initials: E
authors.lastname: Carpenter
authors.forename: Veronica
authors.initials: V
authors.lastname: Valverde-Garduno
authors.forename: Alex
authors.initials: A
authors.lastname: Sternberg
authors.forename: Chris
authors.initials: C
authors.lastname: Mitchell
authors.forename: Irene
authors.initials: I
authors.lastname: Roberts
authors.forename: Paresh
authors.initials: P
authors.lastname: Vyas
authors.forename: Ajay
authors.initials: A
authors.lastname: Vora
mesh_terms: D001483:Base Sequence; D002891:Chromosomes, Human, Pair 21 / Q000235:genetics*; D004252:DNA Mutational Analysis; D004273:DNA, Neoplasm / Q000235:genetics; D004268:DNA-Binding Proteins / Q000235:genetics*; D050981:Erythroid-Specific DNA-Binding Factors; D005260:Female; D050982:GATA1 Transcription Factor; D006801:Humans; D007231:Infant, Newborn; D007947:Leukemia, Megakaryoblastic, Acute / Q000235:genetics; D008297:Male; D008969:Molecular Sequence Data; D009154:Mutation; D009196:Myeloproliferative Disorders / Q000235:genetics*; D009363:Neoplasm Proteins / Q000235:genetics; D014157:Transcription Factors / Q000235:genetics*; D014314:Trisomy
chemical_list: D004273:DNA, Neoplasm; D004268:DNA-Binding Proteins; D050981:Erythroid-Specific DNA-Binding Factors; D050982:GATA1 Transcription Factor; C494688:GATA1 protein, human; D009363:Neoplasm Proteins; D014157:Transcription Factors