Immunogenität von mutations-spezifischen Peptidsequenzen bei der AML

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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.