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.

Simple Summary: Our study describes an AML patient whose leukemia cells carried the NPM1c+ mutation, and who was the recipient of allogeneic HSCT from a haploidentical donor. The patient raised a robust allorestricted CD8+ T cell response directed against the NPM1wt protein. Favourably, the response...

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Publicado en:Current Oncology Vol. 29; no. 5; pp. 2928 - 2935
Autores principales: Nemeckova, Sarka, Alexova-Zurkova, Kamila, Hainz, Petr, Krystofova, Jitka, Mackova, Jana, Roubalova, Katerina, Stastna-Markova, Marketa, Vrana, Milena, Vydra, Jan
Formato: Journal Article
Publicado: MDPI May2022
Acceso en línea:Ver este registro en EBSCOhost
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        10.3390/curroncol29050239
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        atl: 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.
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        au:
          Nemeckova, Sarka
          Alexova-Zurkova, Kamila
          Hainz, Petr
          Krystofova, Jitka
          Mackova, Jana
          Roubalova, Katerina
          Stastna-Markova, Marketa
          Vrana, Milena
          Vydra, Jan
        affil: Institute of Haematology and Blood Transfusion, CZ-128 20 Prague, Czech Republic
      sug:
      ab: Simple Summary: Our study describes an AML patient whose leukemia cells carried the NPM1c+ mutation, and who was the recipient of allogeneic HSCT from a haploidentical donor. The patient 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. 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.
      pubtype: Academic Journal
      doctype: Journal Article
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    language: English
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