Immature forms of low density granulocytes are increased in acute myeloid leukemia and myelodysplastic syndromes

Abstract Neutrophils can promote or suppress tumor growth. These different immunological functions mirror a great heterogenicity of neutrophil maturation and activation status: low-density granulocytes (LDGs) and normal-density neutrophils (NDNs). LDGs participate in immune dysregulation during auto...

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Main Authors: Angela Bertolini, Francesca Picone, Idalucia Ferrara, Anna Maria Della Corte, Bianca Serio, Marisa Gorrese, Annapaola Campana, Vittorio Simeon, Serena Luponio, Rossella Marcucci, Pasqualina Scala, Maddalena Langella, Carmine Selleri, Valentina Giudice
Format: Article
Language:English
Published: Nature Portfolio 2025-03-01
Series:Scientific Reports
Online Access:https://doi.org/10.1038/s41598-025-92513-8
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author Angela Bertolini
Francesca Picone
Idalucia Ferrara
Anna Maria Della Corte
Bianca Serio
Marisa Gorrese
Annapaola Campana
Vittorio Simeon
Serena Luponio
Rossella Marcucci
Pasqualina Scala
Maddalena Langella
Carmine Selleri
Valentina Giudice
author_facet Angela Bertolini
Francesca Picone
Idalucia Ferrara
Anna Maria Della Corte
Bianca Serio
Marisa Gorrese
Annapaola Campana
Vittorio Simeon
Serena Luponio
Rossella Marcucci
Pasqualina Scala
Maddalena Langella
Carmine Selleri
Valentina Giudice
author_sort Angela Bertolini
collection DOAJ
description Abstract Neutrophils can promote or suppress tumor growth. These different immunological functions mirror a great heterogenicity of neutrophil maturation and activation status: low-density granulocytes (LDGs) and normal-density neutrophils (NDNs). LDGs participate in immune dysregulation during autoimmune disorders with an activated phenotype, while NDNs might exert immunosuppressive activities. Here, we investigated variations in distribution of LDGs and NDNs in benign and malignant hematological conditions using an optimized 10-color flow cytometry staining for immunophenotyping of the main circulating populations. A total of 102 consecutive subjects diagnosed with hematological malignancies was enrolled for immunophenotyping by flow cytometry. We showed impaired neutrophil subset distribution in myelodysplastic syndromes (MDS) and acute myeloid leukemia (AML) patients compared to healthy individuals, with intermediate and mature LDGs significantly reduced, also displaying a good diagnostic sensitivity in MDS (AUC, 0.793 and P = 0.0013; and AUC, 0.7319 and P = 0.0109, respectively) and AML (AUC, 0.9059 and P = 0.0069; and AUC, 0.9176 and P = 0.00057, respectively). In conclusion, LDG and NDN subsets could be altered in AML and MDS, in favor of more immature forms, suggesting that emergency hemopoiesis could be a first mechanism to sustain peripheral blood counts, while maintaining a pro-inflammatory microenvironment.
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spelling doaj-art-02a7b9eb9eaf446f8a4e2b0bae6c851c2025-08-20T02:56:12ZengNature PortfolioScientific Reports2045-23222025-03-0115111410.1038/s41598-025-92513-8Immature forms of low density granulocytes are increased in acute myeloid leukemia and myelodysplastic syndromesAngela Bertolini0Francesca Picone1Idalucia Ferrara2Anna Maria Della Corte3Bianca Serio4Marisa Gorrese5Annapaola Campana6Vittorio Simeon7Serena Luponio8Rossella Marcucci9Pasqualina Scala10Maddalena Langella11Carmine Selleri12Valentina Giudice13Department of Medicine, Surgery, and Dentistry, University of SalernoDepartment of Medicine, Surgery, and Dentistry, University of SalernoHematology and Transplant Center, University Hospital “San Giovanni di Dio e Ruggi d’Aragona”Hematology and Transplant Center, University Hospital “San Giovanni di Dio e Ruggi d’Aragona”Hematology and Transplant Center, University Hospital “San Giovanni di Dio e Ruggi d’Aragona”Hematology and Transplant Center, University Hospital “San Giovanni di Dio e Ruggi d’Aragona”Hematology and Transplant Center, University Hospital “San Giovanni di Dio e Ruggi d’Aragona”Department of Mental Health and Public Medicine, Unit of Medical Statistics, University of Campania “Luigi Vanvitelli”Hematology and Transplant Center, University Hospital “San Giovanni di Dio e Ruggi d’Aragona”Hematology and Transplant Center, University Hospital “San Giovanni di Dio e Ruggi d’Aragona”Department of Medicine, Surgery, and Dentistry, University of SalernoHematology and Transplant Center, University Hospital “San Giovanni di Dio e Ruggi d’Aragona”Department of Medicine, Surgery, and Dentistry, University of SalernoDepartment of Medicine, Surgery, and Dentistry, University of SalernoAbstract Neutrophils can promote or suppress tumor growth. These different immunological functions mirror a great heterogenicity of neutrophil maturation and activation status: low-density granulocytes (LDGs) and normal-density neutrophils (NDNs). LDGs participate in immune dysregulation during autoimmune disorders with an activated phenotype, while NDNs might exert immunosuppressive activities. Here, we investigated variations in distribution of LDGs and NDNs in benign and malignant hematological conditions using an optimized 10-color flow cytometry staining for immunophenotyping of the main circulating populations. A total of 102 consecutive subjects diagnosed with hematological malignancies was enrolled for immunophenotyping by flow cytometry. We showed impaired neutrophil subset distribution in myelodysplastic syndromes (MDS) and acute myeloid leukemia (AML) patients compared to healthy individuals, with intermediate and mature LDGs significantly reduced, also displaying a good diagnostic sensitivity in MDS (AUC, 0.793 and P = 0.0013; and AUC, 0.7319 and P = 0.0109, respectively) and AML (AUC, 0.9059 and P = 0.0069; and AUC, 0.9176 and P = 0.00057, respectively). In conclusion, LDG and NDN subsets could be altered in AML and MDS, in favor of more immature forms, suggesting that emergency hemopoiesis could be a first mechanism to sustain peripheral blood counts, while maintaining a pro-inflammatory microenvironment.https://doi.org/10.1038/s41598-025-92513-8
spellingShingle Angela Bertolini
Francesca Picone
Idalucia Ferrara
Anna Maria Della Corte
Bianca Serio
Marisa Gorrese
Annapaola Campana
Vittorio Simeon
Serena Luponio
Rossella Marcucci
Pasqualina Scala
Maddalena Langella
Carmine Selleri
Valentina Giudice
Immature forms of low density granulocytes are increased in acute myeloid leukemia and myelodysplastic syndromes
Scientific Reports
title Immature forms of low density granulocytes are increased in acute myeloid leukemia and myelodysplastic syndromes
title_full Immature forms of low density granulocytes are increased in acute myeloid leukemia and myelodysplastic syndromes
title_fullStr Immature forms of low density granulocytes are increased in acute myeloid leukemia and myelodysplastic syndromes
title_full_unstemmed Immature forms of low density granulocytes are increased in acute myeloid leukemia and myelodysplastic syndromes
title_short Immature forms of low density granulocytes are increased in acute myeloid leukemia and myelodysplastic syndromes
title_sort immature forms of low density granulocytes are increased in acute myeloid leukemia and myelodysplastic syndromes
url https://doi.org/10.1038/s41598-025-92513-8
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