Association of HLA class I type with prevalence and outcome of patients with acute myeloid leukemia and mutated nucleophosmin
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 caucasian 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 concomitantFLT3internal 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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Preprint| Erscheinungsjahr: |
2023 |
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| Erschienen: |
2023 |
| Enthalten in: |
bioRxiv.org - (2023) vom: 04. Sept. Zur Gesamtaufnahme - year:2023 |
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| Sprache: |
Englisch |
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| Beteiligte Personen: |
Kuželová, Kateřina [VerfasserIn] |
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| doi: |
10.1101/411645 |
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| PPN (Katalog-ID): |
XBI000348058 |
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| 245 | 1 | 0 | |a Association of HLA class I type with prevalence and outcome of patients with acute myeloid leukemia and mutated nucleophosmin |
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| 520 | |a 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 caucasian 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 concomitantFLT3internal 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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| 700 | 1 | |a Brodská, Barbora |4 aut | |
| 700 | 1 | |a Schetelig, Johannes |4 aut | |
| 700 | 1 | |a Röllig, Christoph |4 aut | |
| 700 | 1 | |a Ráčil, Zdeněk |4 aut | |
| 700 | 1 | |a Walz, Juliane Stickel |4 aut | |
| 700 | 1 | |a Helbig, Grzegorz |4 aut | |
| 700 | 1 | |a Fuchs, Ota |4 aut | |
| 700 | 1 | |a Vraná, Milena |4 aut | |
| 700 | 1 | |a Pecherková, Pavla |4 aut | |
| 700 | 1 | |a Šálek, Cyril |4 aut | |
| 700 | 1 | |a Mayer, Jiří |4 aut | |
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