Developing a precision medicine approach to target leukaemic stem cells in AML.

开发针对 AML 中的白血病干细胞的精准医学方法。

• 批准号: MR/X030628/1
• 负责人: Anjum Bashir Khan
• 金额: $ 37.25万
• 依托单位: University of York
• 依托单位国家: 英国
• 项目类别: Research Grant
• 财政年份: 2024
• 资助国家: 英国
• 起止时间: 2024 至 无数据
• 项目状态: 未结题
• 来源: https://gtr.ukri.org/projects?ref=MR%2FX030628%2F1
• 关键词: Developing; precision; medicine; approach; target

Acute myeloid leukemia is an aggressive blood cancer with poor outcomes in the majority of patients. The majority of patients are unable to tolerate the intensive chemotherapies offering the prospect of prolonged remissions. Despite chemotherapy, the majority of patients will relapse, and long-term survival is poor once this has occurred. There is therefore an important unmet need to work out why patients relapse, and develop more effective therapies to prevent relapse.We now know that leukaemic stem cells are the underlying reason for resistance to chemotherapy and ultimately relapse. These relatively rare cells are present at diagnosis, and are very different from the majority of leukemia cells. They are not targeted effectively by any current treatments. Proteins are the building blocks of our cells, and are ultimately responsible for how cells behave. Many previous studies have looked in detail at genetic changes in leukemia, but there is a real lack of understanding of how this affects changes to proteins. Recent work has shown that there are lots of differences between leukemia stem cells and other leukaemia cells, which are only seen by looking at proteins rather than genes, and may hold the key to identifying and targeting these cellsThis project plans to identify the particular vulnerabilities of these key cells at a protein level, and use these differences to develop truly targeted and less toxic therapies. The strategy is to develop therapies which protect healthy normal blood stem cells, in contrast to current treatments, reducing the risk of severe infections and the toxic side effects of chemotherapy. This approach has the potential to create a step-change in treatment of AML, opening up opportunities for treating older people safely and effectively despite other health problems, reducing the time people spend in hospital and moving towards home-based treatments which improve both quality of life and long-term survival.

急性髓细胞白血病是一种侵袭性血癌，大多数患者预后不良。大多数患者不能耐受强化化疗，而这种化疗提供了延长缓解的前景。尽管化疗，大多数患者会复发，一旦发生这种情况，长期生存率很低。因此，我们需要找出患者复发的原因，并开发更有效的治疗方法来预防复发。我们现在知道，白血病干细胞是化疗耐药性和最终复发的根本原因。这些相对罕见的细胞在诊断时存在，与大多数白血病细胞非常不同。目前的任何治疗方法都不能有效地靶向它们。蛋白质是我们细胞的基石，并最终负责细胞的行为。许多先前的研究已经详细地研究了白血病的遗传变化，但是对于这如何影响蛋白质的变化缺乏真实的了解。最近的研究表明，白血病干细胞和其他白血病细胞之间存在许多差异，这些差异只能通过蛋白质而不是基因来观察，并且可能是识别和靶向这些细胞的关键，该项目计划在蛋白质水平上识别这些关键细胞的特定脆弱性，并利用这些差异开发真正有针对性和毒性较小的治疗方法。该战略是开发保护健康正常造血干细胞的疗法，与目前的治疗方法相比，降低严重感染的风险和化疗的毒副作用。这种方法有可能在AML的治疗中创造一个台阶式的变化，为安全有效地治疗老年人提供机会，尽管有其他健康问题，减少人们在医院花费的时间，并转向家庭治疗，提高生活质量和长期生存。