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Dynamic Changes in the Ability to Release Neutrophil ExtraCellular Traps in the Course of Childhood Acute Leukemias

Acute leukemias, the most common cancers in children, are characterized by excessive proliferation of malignant progenitor cells. As a consequence of impaired blood cell production, leukemia patients are susceptible to infectious complications—a major cause of non-relapse mortality. Neutrophil extra...

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Autores principales: Ostafin, Magdalena, Ciepiela, Olga, Pruchniak, Michał, Wachowska, Małgorzata, Ulińska, Edyta, Mrówka, Piotr, Głodkowska-Mrówka, Eliza, Demkow, Urszula
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7829911/
https://www.ncbi.nlm.nih.gov/pubmed/33467555
http://dx.doi.org/10.3390/ijms22020821
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author Ostafin, Magdalena
Ciepiela, Olga
Pruchniak, Michał
Wachowska, Małgorzata
Ulińska, Edyta
Mrówka, Piotr
Głodkowska-Mrówka, Eliza
Demkow, Urszula
author_facet Ostafin, Magdalena
Ciepiela, Olga
Pruchniak, Michał
Wachowska, Małgorzata
Ulińska, Edyta
Mrówka, Piotr
Głodkowska-Mrówka, Eliza
Demkow, Urszula
author_sort Ostafin, Magdalena
collection PubMed
description Acute leukemias, the most common cancers in children, are characterized by excessive proliferation of malignant progenitor cells. As a consequence of impaired blood cell production, leukemia patients are susceptible to infectious complications—a major cause of non-relapse mortality. Neutrophil extracellular traps (NETs) are involved in various pathologies, from autoimmunity to cancer. Although aberrant NETs formation may be partially responsible for immune defects observed in acute leukemia, still little is known on the NET release in the course of leukemia. Here, we present the first comprehensive evaluation of NETs formation by neutrophils isolated from children with acute leukemia in different stages of the disease and treatment stimulated in vitro with phorbol 12-myristate 13-acetate (PMA), N-formyl-methionyl-leucyl-phenylalanine (fMLP), and calcium ionophore (CI). NETs release was measured using quantitative fluorescent method and visualized microscopically. In this setting, NETs release was significantly impaired in leukemic children both at the diagnosis and during the treatment, and full restoration of neutrophil function was achieved only after successful completion of the leukemia treatment. We suggest that neutrophil function impairment may result from both disease- and treatment-related factors. In this context, deficient innate immune response observed in acute leukemia patients may be present regardless of neutrophil count and contribute to secondary immunodeficiency observed in this population.
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spelling pubmed-78299112021-01-26 Dynamic Changes in the Ability to Release Neutrophil ExtraCellular Traps in the Course of Childhood Acute Leukemias Ostafin, Magdalena Ciepiela, Olga Pruchniak, Michał Wachowska, Małgorzata Ulińska, Edyta Mrówka, Piotr Głodkowska-Mrówka, Eliza Demkow, Urszula Int J Mol Sci Article Acute leukemias, the most common cancers in children, are characterized by excessive proliferation of malignant progenitor cells. As a consequence of impaired blood cell production, leukemia patients are susceptible to infectious complications—a major cause of non-relapse mortality. Neutrophil extracellular traps (NETs) are involved in various pathologies, from autoimmunity to cancer. Although aberrant NETs formation may be partially responsible for immune defects observed in acute leukemia, still little is known on the NET release in the course of leukemia. Here, we present the first comprehensive evaluation of NETs formation by neutrophils isolated from children with acute leukemia in different stages of the disease and treatment stimulated in vitro with phorbol 12-myristate 13-acetate (PMA), N-formyl-methionyl-leucyl-phenylalanine (fMLP), and calcium ionophore (CI). NETs release was measured using quantitative fluorescent method and visualized microscopically. In this setting, NETs release was significantly impaired in leukemic children both at the diagnosis and during the treatment, and full restoration of neutrophil function was achieved only after successful completion of the leukemia treatment. We suggest that neutrophil function impairment may result from both disease- and treatment-related factors. In this context, deficient innate immune response observed in acute leukemia patients may be present regardless of neutrophil count and contribute to secondary immunodeficiency observed in this population. MDPI 2021-01-15 /pmc/articles/PMC7829911/ /pubmed/33467555 http://dx.doi.org/10.3390/ijms22020821 Text en © 2021 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Ostafin, Magdalena
Ciepiela, Olga
Pruchniak, Michał
Wachowska, Małgorzata
Ulińska, Edyta
Mrówka, Piotr
Głodkowska-Mrówka, Eliza
Demkow, Urszula
Dynamic Changes in the Ability to Release Neutrophil ExtraCellular Traps in the Course of Childhood Acute Leukemias
title Dynamic Changes in the Ability to Release Neutrophil ExtraCellular Traps in the Course of Childhood Acute Leukemias
title_full Dynamic Changes in the Ability to Release Neutrophil ExtraCellular Traps in the Course of Childhood Acute Leukemias
title_fullStr Dynamic Changes in the Ability to Release Neutrophil ExtraCellular Traps in the Course of Childhood Acute Leukemias
title_full_unstemmed Dynamic Changes in the Ability to Release Neutrophil ExtraCellular Traps in the Course of Childhood Acute Leukemias
title_short Dynamic Changes in the Ability to Release Neutrophil ExtraCellular Traps in the Course of Childhood Acute Leukemias
title_sort dynamic changes in the ability to release neutrophil extracellular traps in the course of childhood acute leukemias
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7829911/
https://www.ncbi.nlm.nih.gov/pubmed/33467555
http://dx.doi.org/10.3390/ijms22020821
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