Identification, characterisation and therapeutic targeting of leukaemic stem/propagating cells in Acute Myeloid Leukaemia

急性髓系白血病白血病干细胞/增殖细胞的鉴定、表征和治疗靶向

• 批准号: MC_UU_00016/11
• 负责人: Paresh Vyas
• 金额: $ 176.73万
• 依托单位: University of Oxford
• 依托单位国家: 英国
• 项目类别: Intramural
• 财政年份: 2017
• 资助国家: 英国
• 起止时间: 2017 至 无数据
• 项目状态: 已结题
• 来源: https://gtr.ukri.org/projects?ref=MC_UU_00016%2F11
• 关键词: Identification; characterisation; therapeutic; targeting; leukaemic

There are ~3000 new cases a year in the UK of Acute Myeloid Leukaemia (AML). This is the most common aggressive leukaemia. Despite advances in treating patients under the age of 60 years, 50% of these patients still die of their disease. Furthermore, 80% of patients are over the age of 60 and in this age group only 5% of patients are cured. Thus, we need to improve therapy. AML mainly arises sporadically through acquisition of genetic changes in DNA in multiple genes that regulate the complex process of blood cell production. In some patients there is a preleukaemia condition called Myelodysplasia (MDS). One way to further our understanding AML is to define the compendium of genetic changes throughout all our DNA in both AML and MDS and assess how changes deregulate normal blood stem and progenitor cells and transform them into cancerous populations. This necessary information provides a rational platform for future developments to directly benefit patient care. Furthermore study of MDS and AML provides a model to discover general principles in cancer biology and therapy.

在英国，每年约有3000例急性髓系白血病（AML）新发病例。这是最常见的侵袭性白血病。尽管在治疗60岁以下患者方面取得了进展，但这些患者中仍有50%死于疾病。此外，80%的患者年龄在60岁以上，在这个年龄组中，只有5%的患者治愈。因此，我们需要改进治疗。AML主要通过在调节血细胞产生的复杂过程的多个基因中获得DNA的遗传变化而零星发生。在一些患者中，存在称为骨髓增生异常（MDS）的白血病前期病症。进一步了解AML的一种方法是定义AML和MDS中所有DNA的遗传变化纲要，并评估这些变化如何解除正常造血干细胞和祖细胞的调节，并将其转化为癌细胞群。这些必要的信息为未来的发展提供了一个合理的平台，直接使患者护理受益。此外，MDS和AML的研究提供了发现癌症生物学和治疗的一般原则的模型。

项目成果

MDS-482 Impact Of Magrolimab in Combination With Azacitidine on Red Blood Cells (RBCs) in Patients With Higher-Risk Myelodysplastic Syndromes (HR MDS)

MDS-482 Magrolimab 联合阿扎胞苷对高危骨髓增生异常综合征 (HR MDS) 患者红细胞 (RBC) 的影响

• DOI: 10.1016/s2152-2650(22)01421-5
• 发表时间: 2022
• 期刊: Clinical Lymphoma Myeloma and Leukemia
• 影响因子: 2.7
• 作者: Chen J

Augmented Reduced-Intensity Regimen Does Not Improve Postallogeneic Transplant Outcomes in Acute Myeloid Leukemia.

• DOI: 10.1200/jco.20.02308
• 发表时间: 2021-03-01
• 期刊: Journal of clinical oncology : official journal of the American Society of Clinical Oncology
• 作者: Craddock C;Jackson A;Loke J;Siddique S;Hodgkinson A;Mason J;Andrew G;Nagra S;Malladi R;Peniket A;Gilleece M;Salim R;Tholouli E;Potter V;Crawley C;Wheatley K;Protheroe R;Vyas P;Hunter A;Parker A;Wilson K;Pavlu J;Byrne J;Dillon R;Khan N;McCarthy N;Freeman SD
• 通讯作者: Freeman SD

Oncogenic Drivers and Development.

致癌驱动因素和发展。

• DOI: 10.1158/2159-8290.cd-19-1082
• 发表时间: 2019
• 期刊: Cancer discovery
• 影响因子: 28.2
• 作者: Cruz Hernandez D

New directions for emerging therapies in acute myeloid leukemia: the next chapter.

• DOI: 10.1038/s41408-020-00376-1
• 发表时间: 2020-10-30
• 期刊: Blood cancer journal
• 影响因子: 12.8
• 作者: Daver N;Wei AH;Pollyea DA;Fathi AT;Vyas P;DiNardo CD
• 通讯作者: DiNardo CD

Sensitive, rapid diagnostic test for transient abnormal myelopoiesis and myeloid leukemia of Down syndrome.

针对唐氏综合症的短暂异常骨髓细胞生成和骨髓性白血病的敏感、快速诊断测试。

• DOI: 10.1182/blood.2020005610
• 发表时间: 2020
• 期刊: Blood
• 影响因子: 20.3
• 作者: Cruz Hernandez D