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Altered Spatial Composition of the Immune Cell Repertoire in Association to CD34(+) Blasts in Myelodysplastic Syndromes and Secondary Acute Myeloid Leukemia

SIMPLE SUMMARY: Despite a relationship between immune dysregulation and the course of myelodysplastic syndromes (MDS) has been discussed, a detailed understanding of this phenomenon is still missing. Therefore, multiplex analyses of bone marrow biopsies (BMB) from patients with MDS and secondary acu...

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Autores principales: Bauer, Marcus, Vaxevanis, Christoforos, Al-Ali, Haifa Kathrin, Jaekel, Nadja, Naumann, Christin Le Hoa, Schaffrath, Judith, Rau, Achim, Seliger, Barbara, Wickenhauser, Claudia
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7825771/
https://www.ncbi.nlm.nih.gov/pubmed/33430322
http://dx.doi.org/10.3390/cancers13020186
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author Bauer, Marcus
Vaxevanis, Christoforos
Al-Ali, Haifa Kathrin
Jaekel, Nadja
Naumann, Christin Le Hoa
Schaffrath, Judith
Rau, Achim
Seliger, Barbara
Wickenhauser, Claudia
author_facet Bauer, Marcus
Vaxevanis, Christoforos
Al-Ali, Haifa Kathrin
Jaekel, Nadja
Naumann, Christin Le Hoa
Schaffrath, Judith
Rau, Achim
Seliger, Barbara
Wickenhauser, Claudia
author_sort Bauer, Marcus
collection PubMed
description SIMPLE SUMMARY: Despite a relationship between immune dysregulation and the course of myelodysplastic syndromes (MDS) has been discussed, a detailed understanding of this phenomenon is still missing. Therefore, multiplex analyses of bone marrow biopsies (BMB) from patients with MDS and secondary acute myeloid leukemia (sAML) were performed in order to determine the repertoire of lymphocyte subpopulations and their distance to CD34(+) blasts. In MDS and sAML samples, the composition, quantity, and spatial proximity of immune cell subsets to CD34(+) blasts were heterogeneous and correlated to the blast counts, but not to the genetics of the diseases, while in non-neoplastic BMB no CD8(+) and FOXP3(+) T cells and only single MUM1p(+) B/plasma cells were detected in a distance of ≤10 μm to CD34(+) hematopoietic progenitor cells (HPSC). We conclude that CD8(+) and FOXP3(+) T cells are not part of the immediate surrounding of CD34(+) HPSC. ABSTRACT: Background: Myelodysplastic syndromes (MDS) are caused by a stem cell failure and often include a dysfunction of the immune system. However, the relationship between spatial immune cell distribution within the bone marrow (BM), in relation to genetic features and the course of disease has not been analyzed in detail. Methods: Histotopography of immune cell subpopulations and their spatial distribution to CD34(+) hematopoietic cells was determined by multispectral imaging (MSI) in 147 BM biopsies (BMB) from patients with MDS, secondary acute myeloid leukemia (sAML), and controls. Results: In MDS and sAML samples, a high inter-tumoral immune cell heterogeneity in spatial proximity to CD34(+) blasts was found that was independent of genetic alterations, but correlated to blast counts. In controls, no CD8(+) and FOXP3(+) T cells and only single MUM1p(+) B/plasma cells were detected in an area of ≤10 μm to CD34(+) HSPC. Conclusions: CD8(+) and FOXP3(+) T cells are regularly seen in the 10 μm area around CD34(+) blasts in MDS/sAML regardless of the course of the disease but lack in the surrounding of CD34(+) HSPC in control samples. In addition, the frequencies of immune cell subsets in MDS and sAML BMB differ when compared to control BMB providing novel insights in immune deregulation.
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spelling pubmed-78257712021-01-24 Altered Spatial Composition of the Immune Cell Repertoire in Association to CD34(+) Blasts in Myelodysplastic Syndromes and Secondary Acute Myeloid Leukemia Bauer, Marcus Vaxevanis, Christoforos Al-Ali, Haifa Kathrin Jaekel, Nadja Naumann, Christin Le Hoa Schaffrath, Judith Rau, Achim Seliger, Barbara Wickenhauser, Claudia Cancers (Basel) Article SIMPLE SUMMARY: Despite a relationship between immune dysregulation and the course of myelodysplastic syndromes (MDS) has been discussed, a detailed understanding of this phenomenon is still missing. Therefore, multiplex analyses of bone marrow biopsies (BMB) from patients with MDS and secondary acute myeloid leukemia (sAML) were performed in order to determine the repertoire of lymphocyte subpopulations and their distance to CD34(+) blasts. In MDS and sAML samples, the composition, quantity, and spatial proximity of immune cell subsets to CD34(+) blasts were heterogeneous and correlated to the blast counts, but not to the genetics of the diseases, while in non-neoplastic BMB no CD8(+) and FOXP3(+) T cells and only single MUM1p(+) B/plasma cells were detected in a distance of ≤10 μm to CD34(+) hematopoietic progenitor cells (HPSC). We conclude that CD8(+) and FOXP3(+) T cells are not part of the immediate surrounding of CD34(+) HPSC. ABSTRACT: Background: Myelodysplastic syndromes (MDS) are caused by a stem cell failure and often include a dysfunction of the immune system. However, the relationship between spatial immune cell distribution within the bone marrow (BM), in relation to genetic features and the course of disease has not been analyzed in detail. Methods: Histotopography of immune cell subpopulations and their spatial distribution to CD34(+) hematopoietic cells was determined by multispectral imaging (MSI) in 147 BM biopsies (BMB) from patients with MDS, secondary acute myeloid leukemia (sAML), and controls. Results: In MDS and sAML samples, a high inter-tumoral immune cell heterogeneity in spatial proximity to CD34(+) blasts was found that was independent of genetic alterations, but correlated to blast counts. In controls, no CD8(+) and FOXP3(+) T cells and only single MUM1p(+) B/plasma cells were detected in an area of ≤10 μm to CD34(+) HSPC. Conclusions: CD8(+) and FOXP3(+) T cells are regularly seen in the 10 μm area around CD34(+) blasts in MDS/sAML regardless of the course of the disease but lack in the surrounding of CD34(+) HSPC in control samples. In addition, the frequencies of immune cell subsets in MDS and sAML BMB differ when compared to control BMB providing novel insights in immune deregulation. MDPI 2021-01-07 /pmc/articles/PMC7825771/ /pubmed/33430322 http://dx.doi.org/10.3390/cancers13020186 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
Bauer, Marcus
Vaxevanis, Christoforos
Al-Ali, Haifa Kathrin
Jaekel, Nadja
Naumann, Christin Le Hoa
Schaffrath, Judith
Rau, Achim
Seliger, Barbara
Wickenhauser, Claudia
Altered Spatial Composition of the Immune Cell Repertoire in Association to CD34(+) Blasts in Myelodysplastic Syndromes and Secondary Acute Myeloid Leukemia
title Altered Spatial Composition of the Immune Cell Repertoire in Association to CD34(+) Blasts in Myelodysplastic Syndromes and Secondary Acute Myeloid Leukemia
title_full Altered Spatial Composition of the Immune Cell Repertoire in Association to CD34(+) Blasts in Myelodysplastic Syndromes and Secondary Acute Myeloid Leukemia
title_fullStr Altered Spatial Composition of the Immune Cell Repertoire in Association to CD34(+) Blasts in Myelodysplastic Syndromes and Secondary Acute Myeloid Leukemia
title_full_unstemmed Altered Spatial Composition of the Immune Cell Repertoire in Association to CD34(+) Blasts in Myelodysplastic Syndromes and Secondary Acute Myeloid Leukemia
title_short Altered Spatial Composition of the Immune Cell Repertoire in Association to CD34(+) Blasts in Myelodysplastic Syndromes and Secondary Acute Myeloid Leukemia
title_sort altered spatial composition of the immune cell repertoire in association to cd34(+) blasts in myelodysplastic syndromes and secondary acute myeloid leukemia
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7825771/
https://www.ncbi.nlm.nih.gov/pubmed/33430322
http://dx.doi.org/10.3390/cancers13020186
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