ORIGINAL RESEARCH article
Front. Immunol.
Sec. Cancer Immunity and Immunotherapy
Volume 16 - 2025 | doi: 10.3389/fimmu.2025.1571508
This article is part of the Research TopicPrecision Immunotherapy and Novel Target Discovery in Hematological MalignancyView all 13 articles
Protective effects for HLA-B*40:01 and C*03:04 in NPM1-mutated AML: result of a large HLA association study
Provisionally accepted
Elke Rücker-Braun1,2*
Bose Falk2
Henning Baldauf2Carolin Massalski3
Gesine Schäfer3Heidi Altmann1
Jürgen Sauter4
Ute Verena Solloch4
Vinzenz Lange3Katharina Egger-Heidrich1Desiree Kunadt1
Friedrich Stölzel1Christoph Röllig1Jan Moritz Middeke1
Malte Von Bonin1
Christian Thiede1Alexander H Schmidt2,3,4
Martin Bornhauser1
Johannes Schetelig1,2
Falk Heidenreich1,2- 1Technical University Dresden, Dresden, Germany
- 2Clinical Trials Unit (DKMS), Dresden, Lower Saxony, Germany
- 3DKMS Life Science Lab GmbH, Dresden, Lower Saxony, Germany
- 4DKMS Group, Tuebingen, Germany
Select one of your emails
You have multiple emails registered with Frontiers:
Notify me on publication
Please enter your email address:
If you already have an account, please login
You don't have a Frontiers account ? You can register here
Mutations in the nucleophosmin 1 gene (NPM1) are common and recurrent molecular abnormalities in acute myeloid leukemia (AML). NPM1 mutations are considered to be positive prognostic factors. The beneficial effect may be due to immune responses mediated by cytotoxic T cells targeting HLA presented peptides derived from mutated NPM1 and thereby suppressing mutated NPM1-positive hematopoiesis. While the immunogenicity of these NPM1 peptides has not been demonstrated conclusively, certain HLA-types have been linked to a lower risk of NPM1-mutated AML. In a comprehensive HLA association study at 2-field-resolution, we compared the proportions of HLA class I alleles between NPM1-mutated (n=477) and/or DNMT3A-mutated (n=216) patients with AML and a control group of healthy individuals (n=51,890). We found HLA-B*40:01 and HLA-C*03:04 to be significantly underrepresented in NPM1-mutated AML as compared to the control group (4.0% vs 10.2%, p<0.001, and 8.2% vs 15.9%, p<0.001, respectively). This might suggest that neoepitopes presented by these HLA alleles trigger T-cell responses. Online epitope prediction tools predict that mutated-NPM1 derived peptides bind strongly to B*40:01 and to C*03:04. Based on these findings, further studies should confirm the presence and functionality of neo-epitope specific T cells and characterize specific T-cell receptors (TCR). Sequence information might eventually be exploited in immunotherapeutic approaches to treat AML patients with TCR-engineered T cells or bispecific TCR T/NK cell engagers.
Keywords: AML, nucleophosmin 1, NPM1, DNMT3A R882H, HLA class I
Received: 05 Feb 2025; Accepted: 13 May 2025.
Copyright: © 2025 Rücker-Braun, Falk, Baldauf, Massalski, Schäfer, Altmann, Sauter, Solloch, Lange, Egger-Heidrich, Kunadt, Stölzel, Röllig, Middeke, Von Bonin, Thiede, Schmidt, Bornhauser, Schetelig and Heidenreich. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence: Elke Rücker-Braun, Technical University Dresden, Dresden, Germany
Disclaimer: All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article or claim that may be made by its manufacturer is not guaranteed or endorsed by the publisher.