title: Down syndrome and leukemia: insights into leukemogenesis and translational targets.
abstract: Children with Down syndrome (DS) have a significantly increased risk of childhood leukemia, in particular acute megakaryoblastic leukemia (AMKL) and acute lymphoblastic leukemia (DS-ALL). A pre-leukemia, called transient myeloproliferative disorder (TMD), characterised by a GATA binding protein 1 (GATA1) mutation, affects up to 30% of newborns with DS. In most cases, the pre-leukemia regresses spontaneously, however one-quarter of these children will go on to develop AMKL or myelodysplastic syndrome (MDS) . AMKL and MDS occurring in young children with DS and a GATA1 somatic mutation are collectively termed myeloid leukemia of Down syndrome (ML-DS). This model represents an important multi-step process of leukemogenesis, and further study is required to identify therapeutic targets to potentially prevent development of leukemia. DS-ALL is a high-risk leukemia and mutations in the JAK-STAT pathway are frequently observed. JAK inhibitors may improve outcome for this type of leukemia. Genetic and epigenetic studies have revealed likely candidate drivers involved in development of ML-DS and DS-ALL. Overall this review aims to identify potential impacts of new research on how we manage children with DS, pre-leukemia and leukemia.
authors.affiliation: 1 Kids Cancer Centre, Sydney Children's Hospital, Randwick, Australia ; 2 School of Women's and Children's Health, University of New South Wales, Kensington, Australia ; 3 Children's Cancer Institute Australia, University of New South Wales, Lowy Cancer Centre, Randwick, Australia.
authors.forename: Marion K
authors.initials: MK
authors.lastname: Mateos
authors.affiliation: 1 Kids Cancer Centre, Sydney Children's Hospital, Randwick, Australia ; 2 School of Women's and Children's Health, University of New South Wales, Kensington, Australia ; 3 Children's Cancer Institute Australia, University of New South Wales, Lowy Cancer Centre, Randwick, Australia.
authors.forename: Draga
authors.initials: D
authors.lastname: Barbaric
authors.affiliation: 1 Kids Cancer Centre, Sydney Children's Hospital, Randwick, Australia ; 2 School of Women's and Children's Health, University of New South Wales, Kensington, Australia ; 3 Children's Cancer Institute Australia, University of New South Wales, Lowy Cancer Centre, Randwick, Australia.
authors.forename: Sally-Anne
authors.initials: SA
authors.lastname: Byatt
authors.affiliation: 1 Kids Cancer Centre, Sydney Children's Hospital, Randwick, Australia ; 2 School of Women's and Children's Health, University of New South Wales, Kensington, Australia ; 3 Children's Cancer Institute Australia, University of New South Wales, Lowy Cancer Centre, Randwick, Australia.
authors.forename: Rosemary
authors.initials: R
authors.lastname: Sutton
authors.affiliation: 1 Kids Cancer Centre, Sydney Children's Hospital, Randwick, Australia ; 2 School of Women's and Children's Health, University of New South Wales, Kensington, Australia ; 3 Children's Cancer Institute Australia, University of New South Wales, Lowy Cancer Centre, Randwick, Australia.
authors.forename: Glenn M
authors.initials: GM
authors.lastname: Marshall
keywords: (3-5)-MeSH headings; Down syndrome (DS); children; leukemia; preleukemia; transient myeloproliferative disorder (TMD) of Down syndrome
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