Our aim is to further characterise the molecular and cellular biology of cancer stem cells and to compare and contrast these to normal stem cells. To do so, we utilise malignant and normal haematopoiesis as our model system and use complementary genetic, genomic and functional analyses of both mouse models and primary patient material. We are concentrating on transcriptional alterations in the generation and maintenance of leukaemia stem cells and are examining self-renewal programmes downstream of leukaemia-associated oncogenes and a known self-renewal pathway, the CDX-HOX axis in AML. Furthermore, we are assessing the role of specific genes in the generation and maintenance of leukaemia stem cells, using murine conditional knock-out strains. Our long-term aim is to identify and validate targets which will allow specific treatment of leukaemia and cancer stem cells with acceptable side-effects on normal adult stem cells.