Origins of leukaemia in children with Down syndrome.
Transient megakaryoblastic leukaemia is found in 10% of newborns with Down syndrome, characterized by constitutional trisomy 21. Although in most cases the leukaemic cells disappear spontaneously after the first months of life, irreversible acute megakaryoblastic leukaemia develops in 20% of these individuals within 4 years. The leukaemic cells typically harbour somatic mutations of the gene encoding GATA1, an essential transcriptional regulator of normal megakaryocytic differentiation. Leukaemia that specifically arises in the context of constitutional trisomy 21 and somatic GATA1 mutations is a unique biological model of the incremental process of leukaemic transformation.
Hitzler
Johann K
JK
Department of Pediatrics, Division of Hematology/Oncology, The Hospital for Sick Children, University of Toronto, Ontario, Canada. johann.hitzler@sickkids.ca
Zipursky
Alvin
A
D002471:Cell Transformation, Neoplastic; D002648:Child; D002675:Child, Preschool; D004268:DNA-Binding Proteins / Q000235:genetics; D004314:Down Syndrome / Q000150:complications* / Q000235:genetics; D050981:Erythroid-Specific DNA-Binding Factors; D050982:GATA1 Transcription Factor; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D007947:Leukemia, Megakaryoblastic, Acute / Q000209:etiology* / Q000235:genetics; D014157:Transcription Factors / Q000235:genetics
D004268:DNA-Binding Proteins; D050981:Erythroid-Specific DNA-Binding Factors; D050982:GATA1 Transcription Factor; C494688:GATA1 protein, human; D014157:Transcription Factors