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Non-Mutated Nucleophosmin 1 Is Recognized by the CD8+ T Lymphocytes of an AML Patient after the Transplantation of Hematopoietic Stem Cells from an HLA-Haploidentical Donor
S. Nemeckova, K. Alexova-Zurkova, P. Hainz, J. Krystofova, J. Mackova, K. Roubalova, M. Stastna-Markova, M. Vrana, J. Vydra
Language English Country Switzerland
Document type Journal Article, Research Support, Non-U.S. Gov't
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- MeSH
- Leukemia, Myeloid, Acute * genetics metabolism therapy MeSH
- CD8-Positive T-Lymphocytes metabolism pathology MeSH
- Hematopoietic Stem Cells metabolism pathology MeSH
- Nuclear Proteins genetics metabolism MeSH
- Humans MeSH
- Nucleophosmin * MeSH
- Check Tag
- Humans MeSH
- Publication type
- Journal Article MeSH
- Research Support, Non-U.S. Gov't MeSH
Nucleophosmin (NPM1, B23) is a multifunctional phosphoprotein expressed in all tissues. The protein is mainly localized in nucleoli. In hematological malignancies, NPM1 belongs to commonly altered genes. Its mutation, always heterozygous, leads to the re-localization of the NPM1 protein from the nucleolus to the cytoplasm (NPM1c+). NPM1c+ is found in 30% of acute myeloid leukemia (AML). Our study showed that an AML patient, whose leukemia cells carried the NPM1c+ mutation and who was the recipient of allogeneic HSCT from a haploidentical donor, raised a robust allorestricted CD8+ T cell response directed against the NPM1wt protein. Favourably, the response against NPM1wt was not accompanied by side effects such as GvHD. Moreover, the induction of a high NPM1wt-specific response coincided with the decrease in NPM1c+ transcripts detected, implying a beneficial graft versus leukemia effect. On the basis of these results, we suppose that TCRs from allorestricted NPM1wt-specific T cells are worth studying in other recipients of grafts from haploidentical donors as a possible tool for TCR gene therapy.
References provided by Crossref.org
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