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Association of HLA class I type with prevalence and outcome of patients with acute myeloid leukemia and mutated nucleophosmin

K. Kuželová, B. Brodská, J. Schetelig, C. Röllig, Z. Ráčil, JS. Walz, G. Helbig, O. Fuchs, M. Vraná, P. Pecherková, C. Šálek, J. Mayer,

. 2018 ; 13 (12) : e0204290. [pub] 20181217

Language English Country United States

Document type Clinical Trial, Journal Article, Multicenter Study, Research Support, Non-U.S. Gov't

Persistent link   https://www.medvik.cz/link/bmc19027985

Grant support
NV15-25809A MZ0 CEP Register
NV16-30268A MZ0 CEP Register

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.

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$a Acute myeloid leukemia with mutated nucleophosmin (NPMc+ AML) forms a distinct AML subgroup with better prognosis which can potentially be associated with immune response against the mutated nucleophosmin (NPM). As the T-cell-mediated immunity involves antigen presentation on HLA class I molecules, we hypothesized that individuals with suitable HLA type could be less prone to develop NPMc+ AML. We compared HLA class I distribution in NPMc+ AML patient cohort (398 patients from 5 centers) with the HLA allele frequencies of the healthy population and found HLA-A*02, B*07, B*40 and C*07 underrepresented in the NPMc+ AML group. Presence of B*07 or C*07:01 antigen was associated with better survival in patients without concomitant FLT3 internal tandem duplication. Candidate NPM-derived immunopeptides were found for B*40 and B*07 using prediction software tools. Our findings suggest that a T-cell-mediated immune response could actually explain better prognosis of NPMc+ patients and provide a rationale for attempts to explore the importance of immunosuppressive mechanisms in this AML subgroup.
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$a Brodská, Barbora $u Department of Proteomics, Institute of Hematology and Blood Transfusion, Prague, Czech Republic.
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$a Schetelig, Johannes $u Department of Internal Medicine I, University Hospital Carl Gustav Carus, Dresden, Germany.
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$a Ráčil, Zdeněk $u Department of Internal Medicine-Hematology and Oncology, Masaryk University and University Hospital Brno, Brno, Czech Republic.
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$a Walz, Juliane Stickel $u Department of Hematology and Oncology, University of Tuebingen, Tuebingen, Germany.
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$a Helbig, Grzegorz $u Department of Hematology and Bone Marrow Transplantation, Medical University of Silesia, Katowice, Poland.
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$a Šálek, Cyril $u Clinical Department, Institute of Hematology and Blood Transfusion, Prague, Czech Republic.
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