Open AccessAssociation of HLA class I type with prevalence and outcome of patients with acute myeloid leukemia and mutated nucleophosmin
Author(s) -
Kateřina Kuželová,
Barbora Brodská,
Johannes Schetelig,
Christoph Röllig,
Zdeněk Ráčil,
Juliane S. Walz,
Grzegorz Helbig,
Ota Fuchs,
Milena Vraná,
Pavla Pecherková,
Cyril Šálek,
Jiřı́ Mayer
Publication year - 2018
Publication title -
plos one
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.99
H-Index - 332
ISSN - 1932-6203
DOI - 10.1371/journal.pone.0204290
Subject(s) - nucleophosmin , myeloid leukemia , immunology , human leukocyte antigen , leukemia , immune system , medicine , population , myeloid , oncology , biology , antigen , environmental health
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.