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

正常细胞的生存和生长能力受到严格的控制。癌细胞逃脱了这两种控制，以一种不受管制的方式存活和生长。许多临床使用或临床前开发的疗法都是针对癌细胞的生长。虽然这种方法的优点是在阻止癌细胞生长方面非常有效，但它可能允许一些癌细胞长期存活，并增加这些细胞对药物治疗产生抗药性的可能性，从而导致疾病复发。另一方面，以恶性细胞存活为目标的治疗方法，不管恶性细胞是否生长，都可以杀死它们，从而消除癌症。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。这个装置实际上是一个有2个组件的开关，这两个组件通常都是打开和关闭的。这两个组件以不同的方式连接到传输独特信号的细胞。重要的是，我们发现这种开关在血癌中是错误的，在一些白血病中是永久开启的，从而延长了它们的寿命。靶向这种不受管制的开关的特定成分可能为白血病治疗方法的开发提供新的和改进的方法。

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.