Dr Gordon Strathdee, University of Newcastle
Functional relevance of loss of HOX gene expression in childhood leukaemia
Dr Gordon Strathdee, University of Newcastle; Professor Robert Brown, University of Glasgow; Dr Stefan Meyer, University of Manchester
Award amount: £93,899
Date of award: December 2006
Dr Strathdee and his colleagues are investigating the functional significance of Hox gene inactivation in the development of paediatric leukaemia.
In normal bone marrow a small number of long-lived blood stem cells are constantly generating the huge numbers of cells in the blood. They do this by dividing and then changing and developing – a process known as differentiation.
Once the cells have differentiated they have a finite life-span and no longer divide. Leukaemic cells are stuck in a pre-differentiated state so they carry on dividing and don’t die.
This process of differentiation is controlled in part by a group of genes known as HOX genes, through activation or repression of many other genes.
Dr Strathdee and colleagues have previously identified inactivation of HOX genes during leukaemia development, by a process known as DNA methylation.
This is of particular interest for treatment of leukaemia as a number of drugs are already known that can reverse such gene inactivation by DNA methylation.
In adult leukaemia the team has shown that re-introduction of the HOXA5 gene into leukaemia cells can restore the normal process of differentiation (as can treatment with a drug that reverses DNA methylation).
Importantly, inactivation of HOX genes is most frequently observed in childhood leukaemia.
Dr Strathdee will investigate the importance of this inactivation of HOX genes in causing arrest of normal differentiation in childhood leukaemia and will establish the potential of these genes as targets for therapies that can reverse altered DNA methylation.
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