Role of the Notch signalling pathway in acute myeloid leukaemia

我们正试图确定一种名为Notch的基因在急性白血病中所起的作用。我们已经知道，超过一半的T细胞急性淋巴细胞白血病(T-ALL)儿童存在Notch-1突变，但它们在疾病病因中的作用尚不完全清楚。Notch途径在正常的血细胞生产中扮演着多种角色，在T细胞和血液干细胞的生产中尤为重要。白血病细胞不能发育成正常的血细胞。我们的初步研究表明，一种名为CSL的基因与Notch结合，可能会阻止正常的细胞发育。通过将该基因插入培养中的正常和白血病细胞中，我们希望了解这种情况是如何发生的，以及为什么会发生这种情况。我们还将探索Notch家族其他成员参与白血病发展的可能性。我们特别感兴趣的是，Notch-1突变是否发生在所有年龄段的T-ALL患者中，以及它们是否与T-ALL以外的其他形式的急性白血病有关。这是特别及时的，因为抑制Notch的药物正在开发中，用于治疗T-ALL。。

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. .