Dr Lyndal Kearney, Institute of Cancer Research, London

Children with Down syndrome (DS), the genetic hallmark of which is an extra copy of
chromosome 21, have a greatly increased risk of developing acute leukaemia in the first few years of life.

The leukaemias in DS children are of two distinct kinds. Approximately one half are of a variety that is normally extremely rare - acute megakaryoblastic leukaemia (AMKL).The increased risk for this subtype is some 400-500 times elevated.

The remainder are the common variety (B cell precursor) of acute lymphoblastic leukaemia (ALL), the risk for which is elevated between 10–30 fold.

Recent advances in our understanding of how leukaemia develops in both DS and non-DS children have shown that most cases of childhood leukaemia are initiated by chromosome changes before birth, but require additional mutations to progress to full clinical leukaemia.

Dr Kearney and colleagues have recently identified a specific genetic mutation (JAK2R683) present in around a quarter of DS-ALL cases.

This project aims to determine the developmental timing, cellular targeting and functional significance of the mutation in the development of ALL in children with DS.

This will have an impact not only on our understanding of the very high risk of leukaemia in DS children, but also on the development of childhood ALL in general.

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