Acute myeloid leukemia with mutated nucleophosmin (NPMc+ AML) forms a distinct AML subgroup with better prognosis which can potentially be associated with immune response against the mutated nucleophosmin (NPM). As the T-cell-mediated immunity involves antigen presentation on HLA class I molecules, we hypothesized that individuals with suitable HLA type could be less prone to develop NPMc+ AML. We compared HLA class I distribution in NPMc+ AML patient cohort (398 patients from 5 centers) with the HLA allele frequencies of the healthy population and found HLA-A*02, B*07, B*40 and C*07 underrepresented in the NPMc+ AML group. Presence of B*07 or C*07:01 antigen was associated with better survival in patients without concomitant FLT3 internal tandem duplication. Candidate NPM-derived immunopeptides were found for B*40 and B*07 using prediction software tools. Our findings suggest that a T-cell-mediated immune response could actually explain better prognosis of NPMc+ patients and provide a rationale for attempts to explore the importance of immunosuppressive mechanisms in this AML subgroup.

Clinical Department Institute of Hematology and Blood Transfusion Prague Czech Republic

Department of Genomics Institute of Hematology and Blood Transfusion Prague Czech Republic

Department of Hematology and Bone Marrow Transplantation Medical University of Silesia Katowice Poland

Department of Hematology and Oncology University of Tuebingen Tuebingen Germany

Department of Internal Medicine 1 University Hospital Carl Gustav Carus Dresden Germany

Department of Internal Medicine Hematology and Oncology Masaryk University and University Hospital Brno Brno Czech Republic

Department of Proteomics Institute of Hematology and Blood Transfusion Prague Czech Republic

HLA department Institute of Hematology and Blood Transfusion Prague Czech Republic

Medical Clinic and Policlinic 1 University Hospital Carl Gustav Carus Dresden Germany

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