24 de enero de 2012

Origins of leukaemia in children with Down syndrome


Review

Nature Reviews Cancer 5, 11-20 (January 2005) | doi:10.1038/nrc1525


Origins of leukaemia in children with Down syndrome

Johann K. Hitzler1,2 & Alvin Zipursky1  About the authors
Abstract

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.

1. Department of Pediatrics, Division of Hematology/Oncology, The Hospital for Sick Children, University of Toronto, Toronto, Ontario, Canada.

2. Program in Developmental Biology, The Hospital for Sick Children Research Institute, University of Toronto, Toronto, Ontario, Canada.

Correspondence to: Johann K. Hitzler1,2 Email: johann.hitzler@sickkids.ca