Identification of inflammasome signatures for the prediction of successful treatment-free remission (TFR) in chronic Myeloid Leukaemia

学生奖学金战略优先领域：干细胞ScienceAbstract：慢性粒细胞白血病（CML）是一种血液系统癌症，其特征是造血干细胞的扩增和粒细胞血细胞的不受调节的产生。自引入称为酪氨酸激酶抑制剂（TKI）的靶向治疗以来，CML患者的预后在过去20年中得到了极大的改善，许多患者能够实现分子缓解并具有接近正常的预期寿命。然而，终身使用TKI具有许多生理、心理和经济副作用。有一部分接受TKI治疗的患者可能会停止治疗并达到无治疗缓解（TFR）。这些患者处于深度分子缓解期，但尚不清楚哪些患者能够实现TFR以及原因。该项目将寻找潜在的生物标志物，预测哪些患者是TFR的良好候选人。这将使用从参加DESTINY临床试验的患者中获得的骨髓血浆样本的蛋白质组学分析进行。本试验旨在逐渐减少并最终停止TKI治疗。将比较达到TFR的患者与继续复发的患者在试验入组时的样本。

Studentship strategic priority area: Stem Cell ScienceAbstract: Chronic myeloid leukaemia (CML) is a haematological cancer characterised by expansion of haematopoietic stem cells and unregulated production of granulocytic blood cells. The prognosis of patients with CML has greatly improved over the past 20 years since the introduction of targeted therapies called Tyrosine Kinase Inhibitors (TKIs), with many patients being able to achieve molecular remission and having close to normal life expectancy. However, the lifelong use of TKIs has many physiological, psychological and economic side effects. There is a subset of patients on TKIs, which could potentially stop treatment and achieve treatment-free remission (TFR). These patients are in deep molecular remission however it is not well understood which patients are able to achieve TFR and why. This project will look to identify potential biomarkers that predict which patients are good candidates for TFR. This will be performed using proteomic analysis of bone marrow plasma samples that were obtained from patients who took part in the DESTINY clinical trial. This trial aimed to gradually reduce and eventually stop TKI treatment. Samples at trial entry will be compared for patients who achieved TFR with those who went on to relapse.