title: GATA1 mutations in transient leukemia and acute megakaryoblastic leukemia of Down syndrome.
abstract: Children with constitutional trisomy 21 (Down syndrome) have an approximately 500-fold increased risk of developing acute megakaryoblastic leukemia (AMKL), a form of acute myeloid leukemia. Unique to newborn infants with Down syndrome is a transient leukemia (TL), also referred to as transient myeloproliferative syndrome, that undergoes spontaneous remission in the majority of cases but in approximately 20% is followed by AMKL later in life. Recently mutations of the gene encoding the hematopoietic transcription factor GATA1 were shown to be specific for AMKL of Down syndrome. Here, we demonstrate that GATA1 mutations are present in blasts of TL and show the identical GATA1 mutation in sequential samples collected from a patient during TL and subsequent AMKL. These findings suggest a model of malignant transformation in Down syndrome AMKL in which GATA1 mutations are an early event and AMKL arises from latent TL clones following initial apparent remission.
authors.affiliation: Department of Pediatrics, The Hospital for Sick Children, University of Toronto, ON, Canada. johann.hitzler@sickkids.ca
authors.forename: Johann K
authors.initials: JK
authors.lastname: Hitzler
authors.forename: Joseph
authors.initials: J
authors.lastname: Cheung
authors.forename: Yue
authors.initials: Y
authors.lastname: Li
authors.forename: Stephen W
authors.initials: SW
authors.lastname: Scherer
authors.forename: Alvin
authors.initials: A
authors.lastname: Zipursky
mesh_terms: D002471:Cell Transformation, Neoplastic / Q000235:genetics; D002999:Clone Cells; D004252:DNA Mutational Analysis; D004268:DNA-Binding Proteins / Q000235:genetics*; D004314:Down Syndrome / Q000150:complications*; D050981:Erythroid-Specific DNA-Binding Factors; D005260:Female; D050982:GATA1 Transcription Factor; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D007938:Leukemia / Q000209:etiology / Q000235:genetics; D007947:Leukemia, Megakaryoblastic, Acute / Q000209:etiology / Q000235:genetics*; D008297:Male; D009154:Mutation; D014157:Transcription Factors / Q000235:genetics*
chemical_list: D004268:DNA-Binding Proteins; D050981:Erythroid-Specific DNA-Binding Factors; D050982:GATA1 Transcription Factor; C494688:GATA1 protein, human; D014157:Transcription Factors