Immune responses against the mutated region of cytoplasmatic NPM1 might contribute to the favorable clinical outcome of AML patients with NPM1 mutations (NPM1mut)
To the editor:Immune responses directed against epitopes derived from the mutated region of nucleophosmin 1 (NPM1) by NPM1mut-specific CD8(+) cytotoxic T cells (CTLs) might be involved in the rejection of NPM1mut myeloid leukemic blasts. NPM1 mutations are one of the most frequent molecular alterati...
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| Main Authors: | , , , , , , , |
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| Format: | Article (Journal) Editorial |
| Language: | English |
| Published: |
2013
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| In: |
Blood
Year: 2013, Volume: 122, Issue: 6, Pages: 1087-1088 |
| ISSN: | 1528-0020 |
| DOI: | 10.1182/blood-2013-04-496844 |
| Online Access: | Verlag, lizenzpflichtig, Volltext: https://doi.org/10.1182/blood-2013-04-496844
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| Author Notes: | Jochen Greiner, Vanessa Schneider, Michael Schmitt, Marlies Götz, Konstanze Döhner, Markus Wiesneth, Hartmut Döhner, Susanne Hofmann |
| Summary: | To the editor:Immune responses directed against epitopes derived from the mutated region of nucleophosmin 1 (NPM1) by NPM1mut-specific CD8(+) cytotoxic T cells (CTLs) might be involved in the rejection of NPM1mut myeloid leukemic blasts. NPM1 mutations are one of the most frequent molecular alterations in acute myeloid leukemia (AML) and are an important prognostic marker.1 The mutations cause an abnormal shift of the NPM1 protein from the nucleus to the cytoplasm, described by Falini et al.2 AML patients with NPM1mut, but without FLT3 internal tandem duplication (ITD) mutation, show improved overall survival.3NPM1mut/FLT3-ITD-negative patients do not seem to benefit from allogeneic stem cell transplantation in first-line treatment; however, this issue is still under evaluation, further clinical trials are ongoing, and also minimal residual disease (MRD) has to be considered in treatment decision.3,4 The functional role of NPM1mut for the improved clinical outcome is still under evaluation. Immune responses to NPM1mut may contribute to favorable prognosis of this AML subtype. Recently, we described specific T-cell responses of CD4+ and CD8+ T cells against epitopes derived from mutated regions of NPM1.5 Two NPM1mut-derived peptides, called #1 and #3, induced specific T-cell responses in patients with NPM1mut (33% and 44%, respectively). NPM1mut AML patients showed a significantly higher frequency of CTL responses against peptide #3 compared with healthy volunteers (P = .046).5 Several leukemia-associated antigens (LAAs) have been defined, most importantly RHAMM, Proteinase 3, and Wilms’ tumor antigen 1 (WT-1). These antigens were tested in clinical peptide vaccination trials.6 Immunologic and clinical responses were detected in patients with different hematologic malignancies.7,8 Berneman et al9 discussed NPM1mut as a further important LAA to attack AML and leukemic stem cells by autologous T cells. |
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| Item Description: | Gesehen am 25.02.2020 Im Titel ist "mut" hochgestellt |
| Physical Description: | Online Resource |
| ISSN: | 1528-0020 |
| DOI: | 10.1182/blood-2013-04-496844 |