{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,11,14]],"date-time":"2025-11-14T17:36:30Z","timestamp":1763141790961,"version":"build-2065373602"},"reference-count":26,"publisher":"MDPI AG","issue":"5","license":[{"start":{"date-parts":[[2022,4,20]],"date-time":"2022-04-20T00:00:00Z","timestamp":1650412800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"European Regional Development Fund and the state budget of the Czech Republic, projectAIIHHP","award":["CZ.02.1.01\/0.0\/0.0\/16_025\/0007428 OPRDE MEYS"],"award-info":[{"award-number":["CZ.02.1.01\/0.0\/0.0\/16_025\/0007428 OPRDE MEYS"]}]},{"name":"Ministry of Health, Czech Republic; H CZ - DRO (Institute of Hematology and Blood Tranfusion - IHBT)","award":["IN 00023736"],"award-info":[{"award-number":["IN 00023736"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Current Oncology"],"abstract":"<jats:p>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.<\/jats:p>","DOI":"10.3390\/curroncol29050239","type":"journal-article","created":{"date-parts":[[2022,4,21]],"date-time":"2022-04-21T01:55:51Z","timestamp":1650506151000},"page":"2928-2934","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["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"],"prefix":"10.3390","volume":"29","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-6001-4007","authenticated-orcid":false,"given":"Sarka","family":"Nemeckova","sequence":"first","affiliation":[{"name":"Institute of Haematology and Blood Transfusion, CZ-128 20 Prague, Czech Republic"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0999-880X","authenticated-orcid":false,"given":"Kamila","family":"Alexova-Zurkova","sequence":"additional","affiliation":[{"name":"Institute of Haematology and Blood Transfusion, CZ-128 20 Prague, Czech Republic"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Petr","family":"Hainz","sequence":"additional","affiliation":[{"name":"Institute of Haematology and Blood Transfusion, CZ-128 20 Prague, Czech Republic"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jitka","family":"Krystofova","sequence":"additional","affiliation":[{"name":"Institute of Haematology and Blood Transfusion, CZ-128 20 Prague, Czech Republic"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jana","family":"Mackova","sequence":"additional","affiliation":[{"name":"Institute of Haematology and Blood Transfusion, CZ-128 20 Prague, Czech Republic"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Katerina","family":"Roubalova","sequence":"additional","affiliation":[{"name":"Institute of Haematology and Blood Transfusion, CZ-128 20 Prague, Czech Republic"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Marketa","family":"Stastna-Markova","sequence":"additional","affiliation":[{"name":"Institute of Haematology and Blood Transfusion, CZ-128 20 Prague, Czech Republic"},{"name":"Institute of Clinical and Experimental Hematology, 1st Faculty of Medicine, Charles University, CZ-121 08 Prague, Czech Republic"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6905-6227","authenticated-orcid":false,"given":"Milena","family":"Vrana","sequence":"additional","affiliation":[{"name":"Institute of Haematology and Blood Transfusion, CZ-128 20 Prague, Czech Republic"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jan","family":"Vydra","sequence":"additional","affiliation":[{"name":"Institute of Haematology and Blood Transfusion, CZ-128 20 Prague, Czech Republic"},{"name":"Institute of Clinical and Experimental Hematology, 1st Faculty of Medicine, Charles University, CZ-121 08 Prague, Czech Republic"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2022,4,20]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1707","DOI":"10.1182\/blood.2019004226","article-title":"NPM1-mutated acute myeloid leukemia: From bench to bedside","volume":"136","author":"Falini","year":"2020","journal-title":"Blood"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1186\/s12885-018-4718-6","article-title":"Poor prognosis of nucleophosmin overexpression in solid tumors: A meta-analysis","volume":"18","author":"Chen","year":"2018","journal-title":"BMC Cancer"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"493","DOI":"10.1038\/nrc1885","article-title":"Nucleophosmin and cancer","volume":"6","author":"Grisendi","year":"2006","journal-title":"Nat. Cancer"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"254","DOI":"10.1056\/NEJMoa041974","article-title":"Cytoplasmic Nucleophosmin in Acute Myelogenous Leukemia with a Normal Karyotype","volume":"352","author":"Falini","year":"2005","journal-title":"N. Engl. J. Med."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"2209","DOI":"10.1056\/NEJMoa1516192","article-title":"Genomic Classification and Prognosis in Acute Myeloid Leukemia","volume":"374","author":"Papaemmanuil","year":"2016","journal-title":"N. Engl. J. Med."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"869","DOI":"10.18632\/oncotarget.26617","article-title":"Characterization and dynamics of specific T cells against nucleophosmin-1 (NPM1)-mutated peptides in patients with NPM1-mutated acute myeloid leukemia","volume":"10","author":"Forghieri","year":"2019","journal-title":"Oncotarget"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"1282","DOI":"10.1182\/blood-2011-11-394395","article-title":"Mutated regions of nucleophosmin 1 elicit both CD4+ and CD8+ T-cell responses in patients with acute myeloid leukemia","volume":"120","author":"Greiner","year":"2012","journal-title":"Blood"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"1081","DOI":"10.1182\/blood.V79.4.1081.bloodjournal7941081","article-title":"Nucleolar proteins B23 and C23 as target antigens in chronic graft-versus-host disease","volume":"79","author":"Penner","year":"1992","journal-title":"Blood"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"1124","DOI":"10.1002\/ijc.25133","article-title":"Nucleophosmin is recognized by a cytotoxic T cell line derived from a rectal carcinoma patient","volume":"127","author":"Swoboda","year":"2009","journal-title":"Int. J. Cancer"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"4690","DOI":"10.1172\/JCI88590","article-title":"MHC class I\u2013associated peptides derive from selective regions of the human genome","volume":"126","author":"Pearson","year":"2016","journal-title":"J. Clin. Investig."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"1255","DOI":"10.1074\/mcp.RA119.001524","article-title":"Identification of Tumor Antigens Among the HLA Peptidomes of Glioblastoma Tumors and Plasma","volume":"18","author":"Shraibman","year":"2019","journal-title":"Mol. Cell. Proteom."},{"doi-asserted-by":"crossref","unstructured":"Narayan, R., Olsson, N., Wagar, L.E., Medeiros, B.C., Meyer, E., Czerwinski, D., Khodadoust, M.S., Zhang, L., Schultz, L., and Davis, M.M. (2019). Acute myeloid leukemia immunopeptidome reveals HLA presentation of mutated nucleophosmin. PLoS ONE, 14.","key":"ref_12","DOI":"10.1371\/journal.pone.0219547"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"5615","DOI":"10.1158\/1078-0432.CCR-11-1066","article-title":"PRAME-Specific Allo-HLA\u2013Restricted T Cells with Potent Antitumor Reactivity Useful for Therapeutic T-Cell Receptor Gene Transfer","volume":"17","author":"Amir","year":"2011","journal-title":"Clin. Cancer Res."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"2131","DOI":"10.1182\/blood-2009-03-209387","article-title":"Dendritic cells pulsed with RNA encoding allogeneic MHC and antigen induce T cells with superior antitumor activity and higher TCR functional avidity","volume":"114","author":"Wilde","year":"2009","journal-title":"Blood"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"25","DOI":"10.4049\/jimmunol.162.1.25","article-title":"Alloreactivity as a source of high avidity peptide-specific human CTL","volume":"162","author":"Obst","year":"1999","journal-title":"J. Immunol."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"13114","DOI":"10.1073\/pnas.93.23.13114","article-title":"Peptide-specific cytotoxic T lymphocytes restricted by nonself major histocompatibility complex class I molecules: Reagents for tumor immunotherapy","volume":"93","author":"Sadovnikova","year":"1996","journal-title":"Proc. Natl. Acad. Sci. USA"},{"doi-asserted-by":"crossref","unstructured":"\u0160\u0165astn\u00e1-Markov\u00e1, M., Ham\u0161\u00edkov\u00e1, E., Hainz, P., Hub\u00e1\u010dek, P., Kroutilov\u00e1, M., Kry\u0161tofov\u00e1, J., Ludv\u00edkov\u00e1, V., Musil, J., Pecherkov\u00e1, P., and Sal\u00e1kov\u00e1, M. (2021). Pretransplant BK Virus-Specific T-Cell-Mediated Immunity and Serotype Specific Antibodies May Have Utility in Identifying Patients at Risk of BK Virus-Associated Haemorrhagic Cystitis after Allogeneic HSCT. Vaccines, 9.","key":"ref_17","DOI":"10.1101\/2021.06.09.21258555"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"213","DOI":"10.1007\/s002510050595","article-title":"SYFPEITHI: Database for MHC ligands and peptide motifs","volume":"50","author":"Rammensee","year":"1999","journal-title":"Immunogenetics"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"357","DOI":"10.1007\/s00251-010-0441-4","article-title":"NetCTLpan: Pan-specific MHC class I pathway epitope predictions","volume":"62","author":"Stranzl","year":"2010","journal-title":"Immunogenetics"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"1348","DOI":"10.1111\/ajt.13657","article-title":"Virally-induced heterologous immunity in renal transplant recipients: Important or inconsequential?","volume":"16","author":"Ford","year":"2016","journal-title":"Am. J. Transplant."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"1480","DOI":"10.1111\/ajt.13618","article-title":"Virus-Specific CD8+T Cells Cross-Reactive to Donor-Alloantigen Are Transiently Present in the Circulation of Kidney Transplant Recipients Infected with CMV and\/or EBV","volume":"16","author":"Heutinck","year":"2016","journal-title":"Am. J. Transplant."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"2549","DOI":"10.3389\/fimmu.2019.02549","article-title":"Heterologous Cytomegalovirus and Allo-Reactivity by Shared T Cell Receptor Repertoire in Kidney Transplantation","volume":"10","author":"Stranavova","year":"2019","journal-title":"Front. Immunol."},{"doi-asserted-by":"crossref","unstructured":"Ku\u017eelov\u00e1, K., Brodsk\u00e1, B., Fuchs, O., Dobrovoln\u00e1, M., Soukup, P., and Cetkovsk\u00fd, P. (2015). Altered HLA Class I Profile Associated with Type A\/D Nucleophosmin Mutation Points to Possible Anti-Nucleophosmin Immune Response in Acute Myeloid Leukemia. PLoS ONE, 10.","key":"ref_23","DOI":"10.1371\/journal.pone.0127637"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"3455","DOI":"10.1182\/blood-2014-11-611459","article-title":"Arsenic trioxide and all-trans retinoic acid target NPM1 mutant oncoprotein levels and induce apoptosis in NPM1-mutated AML cells","volume":"125","author":"Martelli","year":"2015","journal-title":"Blood"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"2665","DOI":"10.1080\/15548627.2020.1822628","article-title":"The role of autophagy in targeted therapy for acute myeloid leukemia","volume":"17","author":"Du","year":"2020","journal-title":"Autophagy"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"3204","DOI":"10.1016\/j.celrep.2017.03.018","article-title":"Identification of interleukin-1 by functional screening as a key mediator of cellular expansion and disease progression in acute myeloid leukemia","volume":"18","author":"Carey","year":"2017","journal-title":"Cell Rep."}],"container-title":["Current Oncology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1718-7729\/29\/5\/239\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T22:57:31Z","timestamp":1760137051000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1718-7729\/29\/5\/239"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,4,20]]},"references-count":26,"journal-issue":{"issue":"5","published-online":{"date-parts":[[2022,5]]}},"alternative-id":["curroncol29050239"],"URL":"https:\/\/doi.org\/10.3390\/curroncol29050239","relation":{},"ISSN":["1718-7729"],"issn-type":[{"type":"electronic","value":"1718-7729"}],"subject":[],"published":{"date-parts":[[2022,4,20]]}}}