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.

急性髓样白血病是一种侵略性血液癌，大多数患者的结局较差。大多数患者无法忍受强化化学疗法，从而延长了缓解的前景。尽管化疗，但大多数患者会复发，一旦发生这种情况，长期生存率就很差。因此，要确定为什么患者复发并开发出更有效的疗法以防止复发的重要性，我们现在知道白血病干细胞是对化学疗法抗药性并最终复发的根本原因。这些相对较少的细胞存在于诊断时，与大多数白血病细胞大不相同。当前的任何治疗方法都不是有效的。蛋白质是我们细胞的基础，最终对细胞的行为方式负责。以前的许多研究已经详细研究了白血病的遗传变化，但实际上缺乏对这如何影响蛋白质变化的理解。最近的工作表明，白血病干细胞和其他白血病细胞之间存在很大差异，仅通过查看蛋白质而不是基因来看出，这些细胞可能是识别和靶向这些细胞的关键，以识别和靶向这些细胞的计划，这些计划计划以这些关键细胞在蛋白质水平上识别这些关键细胞的特定脆弱性，并利用这些差异来开发真正的靶向靶向和毒性的毒性治疗。该策略是开发可保护健康正常血干细胞的疗法，与当前的治疗相反，降低了严重感染的风险和化学疗法的毒性副作用。这种方法有可能在治疗AML的治疗方面创造逐步改变，尽管有其他健康问题，也可以为老年人安全有效地治疗老年人提供机会，减少人们在医院的时间，并朝着基于家庭的治疗方向迈进，从而改善生活质量和长期生存。