Role of the Notch signalling pathway in acute myeloid leukaemia

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We are trying to identify the role that a gene called Notch plays in acute leukaemia. We already know that over half of children with T-cell acute lymphoblastic leukaemia (T-ALL) have mutations in Notch-1, but their role in the causation of the disease is not completely understood. The Notch pathway plays several roles in normal blood cell production, being particularly important in the production of T-cells and blood stem cells. Leukaemic cells are unable to develop into normal blood cells. Our preliminary studies suggest that a gene called CSL, which binds to Notch, may prevent normal cell development. By inserting this gene into normal and leukaemic cells in culture, we hope to gain an understanding as to how, and why, this might be the case. We will also explore the possibility that other members of the Notch family are involved in leukaemia development.We are particularly interested in addressing whether Notch-1 mutations occur in all age groups of patients with T-ALL and whether they are involved in other forms of acute leukaemia apart from T-ALL. This is particularly timely as drugs that inhibit Notch are in development for the treatment of T-ALL. .