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The role of a phosphorylated Ser/Tyr bidentate motif in leukemia and myeloproliferative disorders

磷酸化 Ser/Tyr 双齿基序在白血病和骨髓增殖性疾病中的作用

基本信息

批准号：
nhmrc : 430901
负责人：
Dr Mark Guthridge
金额：
$ 18.62万
依托单位：
The University of Adelaide
依托单位国家：
澳大利亚
项目类别：
NHMRC Project Grants
财政年份：
2007
资助国家：
澳大利亚
起止时间：
2007-01-01 至 2009-12-31
项目状态：
已结题

来源：
https://researchdata.edu.au/role-phosphorylated-sertyr-myeloproliferative-disorders/78290
关键词：
role phosphorylated Ser Tyr bidentate

项目摘要

The ability of a normal cell to survive and grow is subject to tight control. Cancer cells escape both these controls and survive and grow in an deregulated manner. Many therapies that are in clinical use or in pre-clinical development target the growth of cancer cells. While such an approach has the advantage of being highly effective in stopping the advance of cancer cell growth, it may allow the long-term survival of some cancer cells and increase the possibility that these cells will become resistant to drug treatment leading to disease relapse. On the other hand, therapies that target the survival of malignant cells would be expected to pull the rug from underneath cancer by killing the malignant cells regardless of whether they are growing or not. We have identified a signalling device in normal blood cells that controls both the growth and survival of cells. This device is in effect a switch with 2 components both of which are normally turned on and off. These 2 components are differentially wired to to the cell transmitting unique signals. Importantly, we have found that this switch is faulty in blood cancers and is permanently on in some leukemias promoting their prolonged life-span. Targetting specific components of this unregulated switch may provide new and improved approaches for the development of therapeutics in the treatment of leukemia.

正常细胞的生存和生长能力受到严格控制。癌细胞逃避这两种控制，并以放松管制的方式生存和生长。临床使用或临床前开发中的许多疗法靶向癌细胞的生长。虽然这种方法具有在阻止癌细胞生长的进展方面非常有效的优点，但它可能允许一些癌细胞的长期存活，并增加这些细胞对药物治疗产生耐药性导致疾病复发的可能性。另一方面，靶向恶性细胞存活的疗法将有望通过杀死恶性细胞而从癌症下面拔出地毯，无论它们是否在生长。我们已经在正常血细胞中发现了一种控制细胞生长和存活的信号装置。该设备实际上是一个开关，具有两个组件，这两个组件通常都打开和关闭。这2个组件以差分方式连接到发送唯一信号的单元。重要的是，我们发现这种开关在血癌中是有缺陷的，在一些白血病中是永久性的，促进了它们的寿命延长。靶向这种不受调节的开关的特定组分可能为开发治疗白血病的疗法提供新的和改进的方法。