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 NPM1(wt) protein. Favourably, the response against NPM1(wt) was not accompanied by side effects such as GvHD. Moreover, the induction of a high NPM1(wt) 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 NPM1(wt)-specific T cells are worth studying in other recipients of grafts from haploidentical donors as a possible tool for TCR gene therapy. ABSTRACT: 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 NPM1(wt) protein. Favourably, the response against NPM1(wt) was not accompanied by side effects such as GvHD. Moreover, the induction of a high NPM1(wt)-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 NPM1(wt)-specific T cells are worth studying in other recipients of grafts from haploidentical donors as a possible tool for TCR gene therapy.