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Correlations Between the Expression of Stromal Cell Activation Related Biomarkers, L-NGFR, Phospho-ERK1-2 and CXCL12, and Primary Myelofibrosis Progression

In myelofibrosis, pathologically enhanced extracellular matrix production due to aberrant cytokine signalling and clonal megakaryocyte functions result(s) in impaired hemopoiesis. Disease progression is still determined by detecting reticulin and collagen fibrosis with Gomori’s silver impregnation....

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Autores principales: Szekely, Tamas, Krenacs, Tibor, Maros, Mate Elod, Bodor, Csaba, Daubner, Viktoria, Csizmadia, Annamaria, Vrabely, Brigitta, Timar, Botond
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8958997/
https://www.ncbi.nlm.nih.gov/pubmed/35356507
http://dx.doi.org/10.3389/pore.2022.1610217
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author Szekely, Tamas
Krenacs, Tibor
Maros, Mate Elod
Bodor, Csaba
Daubner, Viktoria
Csizmadia, Annamaria
Vrabely, Brigitta
Timar, Botond
author_facet Szekely, Tamas
Krenacs, Tibor
Maros, Mate Elod
Bodor, Csaba
Daubner, Viktoria
Csizmadia, Annamaria
Vrabely, Brigitta
Timar, Botond
author_sort Szekely, Tamas
collection PubMed
description In myelofibrosis, pathologically enhanced extracellular matrix production due to aberrant cytokine signalling and clonal megakaryocyte functions result(s) in impaired hemopoiesis. Disease progression is still determined by detecting reticulin and collagen fibrosis with Gomori’s silver impregnation. Here, we tested whether the expression growth related biomarkers L-NGFR/CD271, phospho-ERK1-2 and CXCL12 can be linked to the functional activation of bone marrow stromal cells during primary myelofibrosis progression. Immunoscores for all tested biomarkers showed varying strength of positive statistical correlation with the silver impregnation based myelofibrosis grades. The intimate relationship between spindle shaped stromal cells positive for all three markers and aberrant megakaryocytes was likely to reflect their functional cooperation. L-NGFR reaction was restricted to bone marrow stromal cells and revealed the whole length of their processes. Also, L-NGFR positive cells showed the most intersections, the best statistical correlations with myelofibrosis grades and the strongest interrater agreements. CXCL12 reaction highlighted stromal cell bodies and a weak extracellular staining in line with its constitutive release. Phospho-ERK1-2 reaction showed a similar pattern to CXCL12 in stromal cells with an additional nuclear staining in agreement with its role as a transcription factor. Both p-ERK1-2 and CXCL12 were also expressed at a moderate level in sinus endothelial cells. Connexin 43 gap junction communication channels, known to be required for CXCL12 release to maintain stem cell niche, were also expressed progressively in the myelofibrotic stromal network as a support of compartmental functions. Our results suggest that, diverse growth related pathways are activated in the functionally coupled bone marrow stromal cells during myelofibrosis progression. L-NGFR expression can be a useful biological marker of stromal cell activation which deserves diagnostic consideration for complementing Gomori’s silver impregnation.
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spelling pubmed-89589972022-03-29 Correlations Between the Expression of Stromal Cell Activation Related Biomarkers, L-NGFR, Phospho-ERK1-2 and CXCL12, and Primary Myelofibrosis Progression Szekely, Tamas Krenacs, Tibor Maros, Mate Elod Bodor, Csaba Daubner, Viktoria Csizmadia, Annamaria Vrabely, Brigitta Timar, Botond Pathol Oncol Res Pathology and Oncology Archive In myelofibrosis, pathologically enhanced extracellular matrix production due to aberrant cytokine signalling and clonal megakaryocyte functions result(s) in impaired hemopoiesis. Disease progression is still determined by detecting reticulin and collagen fibrosis with Gomori’s silver impregnation. Here, we tested whether the expression growth related biomarkers L-NGFR/CD271, phospho-ERK1-2 and CXCL12 can be linked to the functional activation of bone marrow stromal cells during primary myelofibrosis progression. Immunoscores for all tested biomarkers showed varying strength of positive statistical correlation with the silver impregnation based myelofibrosis grades. The intimate relationship between spindle shaped stromal cells positive for all three markers and aberrant megakaryocytes was likely to reflect their functional cooperation. L-NGFR reaction was restricted to bone marrow stromal cells and revealed the whole length of their processes. Also, L-NGFR positive cells showed the most intersections, the best statistical correlations with myelofibrosis grades and the strongest interrater agreements. CXCL12 reaction highlighted stromal cell bodies and a weak extracellular staining in line with its constitutive release. Phospho-ERK1-2 reaction showed a similar pattern to CXCL12 in stromal cells with an additional nuclear staining in agreement with its role as a transcription factor. Both p-ERK1-2 and CXCL12 were also expressed at a moderate level in sinus endothelial cells. Connexin 43 gap junction communication channels, known to be required for CXCL12 release to maintain stem cell niche, were also expressed progressively in the myelofibrotic stromal network as a support of compartmental functions. Our results suggest that, diverse growth related pathways are activated in the functionally coupled bone marrow stromal cells during myelofibrosis progression. L-NGFR expression can be a useful biological marker of stromal cell activation which deserves diagnostic consideration for complementing Gomori’s silver impregnation. Frontiers Media S.A. 2022-03-14 /pmc/articles/PMC8958997/ /pubmed/35356507 http://dx.doi.org/10.3389/pore.2022.1610217 Text en Copyright © 2022 Szekely, Krenacs, Maros, Bodor, Daubner, Csizmadia, Vrabely and Timar. https://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 Pathology and Oncology Archive
Szekely, Tamas
Krenacs, Tibor
Maros, Mate Elod
Bodor, Csaba
Daubner, Viktoria
Csizmadia, Annamaria
Vrabely, Brigitta
Timar, Botond
Correlations Between the Expression of Stromal Cell Activation Related Biomarkers, L-NGFR, Phospho-ERK1-2 and CXCL12, and Primary Myelofibrosis Progression
title Correlations Between the Expression of Stromal Cell Activation Related Biomarkers, L-NGFR, Phospho-ERK1-2 and CXCL12, and Primary Myelofibrosis Progression
title_full Correlations Between the Expression of Stromal Cell Activation Related Biomarkers, L-NGFR, Phospho-ERK1-2 and CXCL12, and Primary Myelofibrosis Progression
title_fullStr Correlations Between the Expression of Stromal Cell Activation Related Biomarkers, L-NGFR, Phospho-ERK1-2 and CXCL12, and Primary Myelofibrosis Progression
title_full_unstemmed Correlations Between the Expression of Stromal Cell Activation Related Biomarkers, L-NGFR, Phospho-ERK1-2 and CXCL12, and Primary Myelofibrosis Progression
title_short Correlations Between the Expression of Stromal Cell Activation Related Biomarkers, L-NGFR, Phospho-ERK1-2 and CXCL12, and Primary Myelofibrosis Progression
title_sort correlations between the expression of stromal cell activation related biomarkers, l-ngfr, phospho-erk1-2 and cxcl12, and primary myelofibrosis progression
topic Pathology and Oncology Archive
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8958997/
https://www.ncbi.nlm.nih.gov/pubmed/35356507
http://dx.doi.org/10.3389/pore.2022.1610217
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