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Lack of Viral Load Within Chronic Lymphoproliferative Disorder of Natural Killer Cells: What Is Outside the Leukemic Clone?

Large granular lymphocyte leukemias (LGLL) are sustained by proliferating cytotoxic T cells or NK cells, as happens in Chronic Lymphoproliferative Disorder of Natural Killer cells (CLPD-NK), whose etiology is only partly understood. Different hypotheses have been proposed on the original events trig...

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Autores principales: Giussani, Edoardo, Binatti, Andrea, Calabretto, Giulia, Gasparini, Vanessa Rebecca, Teramo, Antonella, Vicenzetto, Cristina, Barilà, Gregorio, Facco, Monica, Coppe, Alessandro, Semenzato, Gianpietro, Bortoluzzi, Stefania, Zambello, Renato
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7873950/
https://www.ncbi.nlm.nih.gov/pubmed/33585237
http://dx.doi.org/10.3389/fonc.2020.613570
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author Giussani, Edoardo
Binatti, Andrea
Calabretto, Giulia
Gasparini, Vanessa Rebecca
Teramo, Antonella
Vicenzetto, Cristina
Barilà, Gregorio
Facco, Monica
Coppe, Alessandro
Semenzato, Gianpietro
Bortoluzzi, Stefania
Zambello, Renato
author_facet Giussani, Edoardo
Binatti, Andrea
Calabretto, Giulia
Gasparini, Vanessa Rebecca
Teramo, Antonella
Vicenzetto, Cristina
Barilà, Gregorio
Facco, Monica
Coppe, Alessandro
Semenzato, Gianpietro
Bortoluzzi, Stefania
Zambello, Renato
author_sort Giussani, Edoardo
collection PubMed
description Large granular lymphocyte leukemias (LGLL) are sustained by proliferating cytotoxic T cells or NK cells, as happens in Chronic Lymphoproliferative Disorder of Natural Killer cells (CLPD-NK), whose etiology is only partly understood. Different hypotheses have been proposed on the original events triggering NK cell hyperactivation and transformation, including a role of viral agents. In this perspective, we revise the lines of evidence that suggested a pathogenetic role in LGLL of the exposure to retroviruses and that identified Epstein Barr Virus (EBV) in other NK cell leukemias and lymphomas and focus on the contrasting data about the importance of viral agents in CLPD-NK. EBV was detected in aggressive NK leukemias but not in the indolent CLPD-NK, where seroreactivity against HTLV-1 retrovirus envelope BA21 protein antigens has been reported in patients, although lacking clear evidence of HTLV infection. We next present original results of whole exome sequencing data analysis that failed to identify viral sequences in CLPD-NK. We recently demonstrated that proliferating NK cells of patients harbor several somatic lesions likely contributing to sustain NK cell proliferation. Thus, we explore whether “neoantigens” similar to the BA21 antigen could be generated by aberrancies present in the leukemic clone. In light of the literature and new data, we evaluated the intriguing hypothesis that NK cell activation can be caused by retroviral agents located outside the hematopoietic compartment and on the possible mechanisms involved with the prospects of immunotherapy-based approaches to limit the growth of NK cells in CLPD-NK disease.
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spelling pubmed-78739502021-02-11 Lack of Viral Load Within Chronic Lymphoproliferative Disorder of Natural Killer Cells: What Is Outside the Leukemic Clone? Giussani, Edoardo Binatti, Andrea Calabretto, Giulia Gasparini, Vanessa Rebecca Teramo, Antonella Vicenzetto, Cristina Barilà, Gregorio Facco, Monica Coppe, Alessandro Semenzato, Gianpietro Bortoluzzi, Stefania Zambello, Renato Front Oncol Oncology Large granular lymphocyte leukemias (LGLL) are sustained by proliferating cytotoxic T cells or NK cells, as happens in Chronic Lymphoproliferative Disorder of Natural Killer cells (CLPD-NK), whose etiology is only partly understood. Different hypotheses have been proposed on the original events triggering NK cell hyperactivation and transformation, including a role of viral agents. In this perspective, we revise the lines of evidence that suggested a pathogenetic role in LGLL of the exposure to retroviruses and that identified Epstein Barr Virus (EBV) in other NK cell leukemias and lymphomas and focus on the contrasting data about the importance of viral agents in CLPD-NK. EBV was detected in aggressive NK leukemias but not in the indolent CLPD-NK, where seroreactivity against HTLV-1 retrovirus envelope BA21 protein antigens has been reported in patients, although lacking clear evidence of HTLV infection. We next present original results of whole exome sequencing data analysis that failed to identify viral sequences in CLPD-NK. We recently demonstrated that proliferating NK cells of patients harbor several somatic lesions likely contributing to sustain NK cell proliferation. Thus, we explore whether “neoantigens” similar to the BA21 antigen could be generated by aberrancies present in the leukemic clone. In light of the literature and new data, we evaluated the intriguing hypothesis that NK cell activation can be caused by retroviral agents located outside the hematopoietic compartment and on the possible mechanisms involved with the prospects of immunotherapy-based approaches to limit the growth of NK cells in CLPD-NK disease. Frontiers Media S.A. 2021-01-18 /pmc/articles/PMC7873950/ /pubmed/33585237 http://dx.doi.org/10.3389/fonc.2020.613570 Text en Copyright © 2021 Giussani, Binatti, Calabretto, Gasparini, Teramo, Vicenzetto, Barilà, Facco, Coppe, Semenzato, Bortoluzzi and Zambello http://creativecommons.org/licenses/by/4.0/ 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) and the copyright owner(s) 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.
spellingShingle Oncology
Giussani, Edoardo
Binatti, Andrea
Calabretto, Giulia
Gasparini, Vanessa Rebecca
Teramo, Antonella
Vicenzetto, Cristina
Barilà, Gregorio
Facco, Monica
Coppe, Alessandro
Semenzato, Gianpietro
Bortoluzzi, Stefania
Zambello, Renato
Lack of Viral Load Within Chronic Lymphoproliferative Disorder of Natural Killer Cells: What Is Outside the Leukemic Clone?
title Lack of Viral Load Within Chronic Lymphoproliferative Disorder of Natural Killer Cells: What Is Outside the Leukemic Clone?
title_full Lack of Viral Load Within Chronic Lymphoproliferative Disorder of Natural Killer Cells: What Is Outside the Leukemic Clone?
title_fullStr Lack of Viral Load Within Chronic Lymphoproliferative Disorder of Natural Killer Cells: What Is Outside the Leukemic Clone?
title_full_unstemmed Lack of Viral Load Within Chronic Lymphoproliferative Disorder of Natural Killer Cells: What Is Outside the Leukemic Clone?
title_short Lack of Viral Load Within Chronic Lymphoproliferative Disorder of Natural Killer Cells: What Is Outside the Leukemic Clone?
title_sort lack of viral load within chronic lymphoproliferative disorder of natural killer cells: what is outside the leukemic clone?
topic Oncology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7873950/
https://www.ncbi.nlm.nih.gov/pubmed/33585237
http://dx.doi.org/10.3389/fonc.2020.613570
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