The role of MYBL2 in the age-related development of blood disorders

我们在一生中维持健康功能性血细胞供应的能力绝对依赖于我们骨髓中存在的特化干细胞。像体内的其他干细胞一样，这些血液干细胞可以根据需要提供成熟细胞的供应，同时能够复制自己，使它们在整个生命中不会耗尽。随着年龄的增长，血液干细胞可以逐渐获得其遗传物质的突变，有时会导致血液疾病的出现，其中正常数量的血细胞类型被破坏或白血病的出现。我们知道，在细胞分裂时，一种蛋白质对限制遗传损伤至关重要，这种蛋白质被称为MYBL 2，编码这种蛋白质的基因的丢失似乎与某些与年龄有关的血液疾病和白血病有关。我已经建立了一个小鼠模型，模拟了MYBL 2在一些血液疾病患者中的改变方式，我希望用它来研究干细胞中这种蛋白质的变化在我们变老时会导致血液疾病的确切方式。该项目的成果将提供新的信息，以帮助诊断和预后，并可能导致白血病和与年龄相关的干细胞功能下降的新疗法。

Our ability to maintain a supply of healthy functional blood cells throughout our lives is absolutely dependent on the presence in our bone marrow of specialized stem cells. Like other stem cells in the body, these blood stem cells serve to provide a supply of mature cells as required and at the same time are able to make copies of themselves so that they do not become depleted throughout life. As we age, the blood stem cells can gradually acquire mutations in their genetic material sometimes leading to the appearance either of blood disorders in which either the normal number of type of blood cells produced is disrupted or a leukaemia arises. A protein that we know to be critical to limit genetic damage as cells divide is known as MYBL2, and loss of the gene coding for this appears to be linked to certain age-related blood disorders and leukaemia. I have generated a mouse model mimicking the way in which MYBL2 is altered in some patients with blood disorders and I wish to use this to study the precise way in which changes in this protein in stem cells can cause blood diseases as we get older. The outcomes of the project should provide new information to aid diagnosis and prognosis, and may lead to novel treatments for leukaemia and age-related decline in stem cell function.