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.

急性髓系白血病是一种侵袭性血癌，大多数患者预后不佳。大多数患者无法耐受强化化疗，而这提供了长期缓解的前景。尽管进行化疗，大多数患者仍会复发，一旦发生，长期生存率很差。因此，迫切需要弄清楚患者复发的原因，并开发更有效的疗法来预防复发。我们现在知道，白血病干细胞是化疗耐药并最终复发的根本原因。这些相对罕见的细胞在诊断时就存在，并且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针对它们。蛋白质是我们细胞的组成部分，并最终决定细胞的行为。之前的许多研究都详细研究了白血病的基因变化，但对其如何影响蛋白质的变化确实缺乏了解。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多差异，这些差异只能通过观察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。该项目计划识别这些关键细胞在蛋白质水平上，并利用这些差异来开发真正有针对性且毒性较小的疗法。该策略是开发与现有治疗方法不同的保护健康正常血液干细胞的疗法，从而降低严重感染的风险和化疗的毒副作用。这种方法有可能使 AML 的治疗发生巨大变化，为安全有效地治疗老年人（尽管存在其他健康问题）提供机会，减少人们在医院的时间，并转向家庭治疗，从而提高治疗质量生命和长期生存。