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

Kateřina Kuželová; Barbora Brodská; Johannes Schetelig; Christoph Röllig; Zdeněk Ráčil; Juliane Stickel Walz; Grzegorz Helbig; Ota Fuchs; Milena Vraná; Pavla Pecherková; Cyril Šálek; Jiří Mayer

doi:10.1371/journal.pone.0204290

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

PLoS One. 2018 Dec 17;13(12):e0204290. doi: 10.1371/journal.pone.0204290. eCollection 2018.

Authors

Affiliations

¹ Department of Proteomics, Institute of Hematology and Blood Transfusion, Prague, Czech Republic.
² Department of Internal Medicine I, University Hospital Carl Gustav Carus, Dresden, Germany.
³ Medical Clinic and Policlinic I, University Hospital Carl Gustav Carus, Dresden, Germany.
⁴ Department of Internal Medicine-Hematology and Oncology, Masaryk University and University Hospital Brno, Brno, Czech Republic.
⁵ Department of Hematology and Oncology, University of Tuebingen, Tuebingen, Germany.
⁶ Department of Hematology and Bone Marrow Transplantation, Medical University of Silesia, Katowice, Poland.
⁷ Department of Genomics, Institute of Hematology and Blood Transfusion, Prague, Czech Republic.
⁸ HLA department, Institute of Hematology and Blood Transfusion, Prague, Czech Republic.
⁹ Clinical Department, Institute of Hematology and Blood Transfusion, Prague, Czech Republic.

Abstract

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.

Publication types

Clinical Trial
Multicenter Study
Research Support, Non-U.S. Gov't

MeSH terms

Adult
Aged
Disease-Free Survival
Female
Histocompatibility Antigens Class I* / genetics
Histocompatibility Antigens Class I* / immunology
Humans
Immunity, Cellular*
Leukemia, Myeloid, Acute* / genetics
Leukemia, Myeloid, Acute* / immunology
Leukemia, Myeloid, Acute* / mortality
Male
Middle Aged
Neoplasm Proteins* / genetics
Neoplasm Proteins* / immunology
Nuclear Proteins* / genetics
Nuclear Proteins* / immunology
Nucleophosmin
Prevalence
Survival Rate
T-Lymphocytes / immunology*

Substances

Histocompatibility Antigens Class I
NPM1 protein, human
Neoplasm Proteins
Nuclear Proteins
Nucleophosmin

Grants and funding

The work has been conducted with financial support from the Ministry of Health of the Czech Republic (grant No 16-30268A to KK, grant No 15-25809A to ZR and the project for conceptual development of the research organization No 00023736), European Regional Development Fund and the state budget of the Czech Republic (project AIIHHP: CZ.02.1.01/0.0/0.0/16_025/0007428, OP RDE, Ministry of Education, Youth and Sports). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.