AIMS: This study aimed to examine changes in the repertoire of functional T-cells specific for six leukemia-associated antigens (LAA), including WT1, PRAME, MUC1, CCNA1, NPM1, and NPM1c, during immune reconstitution following allogeneic transplantation of hematopoietic stem cells (HSCT) in patients with acute myeloid leukemia. PATIENTS & METHODS: LAA-specific T cell response was measured by ELISPOT- IFNγ and intracellular cytokine staining in 47 patients before starting conditioning therapy (baseline) and 7 months after HSCT. RESULTS: The positive cumulative LAA-specific T cell response before HSCT was associated with a decreased risk of relapse after HSCT. The prevalent genetic aberration - an internal tandem duplication of Fms 3 - related receptor tyrosine kinase, which has been previously implicated in immune escape mechanisms, is presented here for the first time as a factor associated with the absence of an adaptive T cell response against multiple LAAs. T-cell specific responses against wild-type and mutated NPM1 antigens were less frequent in the study cohort and did not correlate with mutations in the NPM1 gene. CONCLUSIONS: Our results showed that the T-cell response to LAA can be reconstituted after HSCT. Measurement of functional pre-transplant T-cell responses against multiple LAAs could help to find patients with an increased risk of relapse.

• Keywords
• ELISPOT-interferon gamma, Flt3-ITD, Leukemia associated antigen, T cell response, acute myeloid leukemia, hematopoietic stem cell transplantation, relapse,
• MeSH
• Leukemia, Myeloid, Acute * therapy   genetics   immunology   MeSH
• Antigens, Neoplasm immunology   MeSH
• Adult MeSH
• Transplantation, Homologous MeSH
• Nuclear Proteins genetics   MeSH
• Middle Aged MeSH
• Humans MeSH
• Adolescent MeSH
• Young Adult MeSH
• Mutation MeSH
• Nucleophosmin MeSH
• Recurrence MeSH
• Aged MeSH
• T-Lymphocytes * immunology   MeSH
• Hematopoietic Stem Cell Transplantation * MeSH
• fms-Like Tyrosine Kinase 3 * genetics   MeSH
• Check Tag
• Adult MeSH
• Middle Aged MeSH
• Humans MeSH
• Adolescent MeSH
• Young Adult MeSH
• Male MeSH
• Aged MeSH
• Female MeSH
• Publication type
• Journal Article MeSH
• Research Support, Non-U.S. Gov't MeSH
• Names of Substances
• Antigens, Neoplasm MeSH
• FLT3 protein, human MeSH Browser
• Nuclear Proteins MeSH
• NPM1 protein, human MeSH Browser
• Nucleophosmin MeSH
• fms-Like Tyrosine Kinase 3 * MeSH