Immunogenität von mutations-spezifischen Peptidsequenzen bei der AML

考虑到资助的项目，我们能够证明对来自NPM1突变区域的表位的免疫应答，NPM1是AML中最常见的突变之一。在具有NPM 1突变的AML患者中检测到约40%的高数目的NPM 1特异性免疫应答。在同种异体干细胞移植和供体淋巴细胞输注后，我们也可以显示针对来自NPM 1突变区域的肽的免疫应答。在一小组患者中，我们发现与没有免疫反应的患者相比，对NPM1特异性表位有免疫反应的患者总体生存率更高。可能检测到的免疫应答对AML患者的生存有影响，并解释了已知的具有NPM1突变的AML患者的更好预后。在该扩增要求中，将在更大的患者群体中分析所证明的免疫应答，将表征用FACS进行的T细胞亲合力分析以及针对NPM 1突变患者的白血病祖细胞的免疫反应。此外，还将描述异基因干细胞移植和供体淋巴细胞输注过程中针对NPM1表位的免疫应答。除了NPM1突变特异性肽外，还将分析其他突变衍生的表位，如ckit和nras。

Accounting the aided project we were able to demonstrate immune responses against epitopes derived from the mutated region of NPM1, one of the most frequent mutations in AML. With a high number of about 40 % NPM1-specific immune responses were detected in patients with AML with NPM1 mutation. After allogeneic stem cell transplantation and donor lymphocyte infusion we could also show immune responses against peptides derived from the NPM1-mutated region. In a small group of patients we found a trend for better overall survival in patients who hold a immune response against NPM1-specific epitopes compared to those without immune reactions. Possibly the detected immune responses have an impact on survival of AML patients and explain the already known better prognosis of AML patients with NPM1 mutation. Within this request of expansion the demonstrated immune responses are going to be analysed in a larger population of patients, avidity analysis of the T cells with FACS are going to be characterized as well as immune reactions against leukemic progenitor cells of NPM1 mutated patients. In addition immune responses against the NPM1 epitopes during the course of allogeneic stem cell transplantation and donor lymphocyte infusion are going to be described. Besides the NPM1 mutation specific peptides other mutation-derived epitopes are going to be analysed, such as ckit and nras.