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The Hox family of homeodomain transcription factors are essential for the regulation of hematopoiesis and deregulated expression of some Hox gene is associated with the development of myeloproliferative disorders and leukaemia.In mammals, 39 Hox genes are organized into four clusters (A, B, C or D).The expression of these genes is tightly regulated at particular differentiation points in haematopoiesis.Importantly, overexpression of Hox genes such as HoxA9 and HoxA10 are associated with poor prognosis of acute myeloid leukaemia.Overexpression of murine HoxB8 together with IL-3 results in myeloid leukaemia in mice.The mechanisms of action of Hox proteins in leukaemiagenesis remain to be determined but are thought to result from a block in myeloid differentiation.We have previously used HoxB8 to immortalise IL-3 dependent myeloid progenitor cells derived from mice lacking one or more genes in the cell death pathway to determine which genes are required for apoptosis provoked by IL-3 deprivation.We are now investigating the molecular mechanisms by which Hox genes, in particular HoxB8 and HoxA9 contribute to immortalisation of growth factor dependent myeloid cell lines in order to determine how the genes may contribute to leukaemic transformation.