Immunogenität von mutations-spezifischen Peptidsequenzen bei der AML

考虑到辅助项目，我们能够展示对来自NPM1突变区域的表位的免疫反应，NPM1突变区域是AML中最常见的突变之一。在具有NPM1突变的AML患者中检测到高达约40%的NPM1特异性免疫反应。在异基因干细胞移植和供者淋巴细胞输注后，我们也可以对来自NPM1突变区域的多肽产生免疫反应。在一小部分患者中，我们发现，与那些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存活率更高。检测到的免疫反应可能对AML患者的生存有影响，并解释了已知的NPM1突变AML患者预后较好的原因。在这一扩大的要求下，将在更大的患者群体中分析所展示的免疫反应，将用FACS对T细胞的亲和力分析以及针对NPM1突变患者的白血病祖细胞的免疫反应进行表征。此外，还将描述在异基因干细胞移植和供体淋巴细胞输注过程中针对NPM1表位的免疫反应。除了NPM1突变特异性多肽外，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.