Down syndrome and leukemia: insights into leukemogenesis and translational targets

Translational Pediatrics
Marion K MateosGlenn M Marshall

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.

Citations

Aug 19, 2017·Cellular and Molecular Life Sciences : CMLS·Camille Malouf, Katrin Ottersbach
Sep 17, 2020·Oncotarget·Mariana PerepitchkaVasiliy Galat
Aug 31, 2019·Neonatal Network : NN·Larissa Gallaway, Amy J Jnah
Jun 18, 2021·Frontiers in Cell and Developmental Biology·Iveta GažováKim M Summers
Aug 7, 2021·Brain Sciences·Hanani Abdul Manan, Noorazrul Yahya

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