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The presence of CXCR4(+) CD1a(+) cells at onset of Langerhans cell histiocytosis is associated with a less favorable outcome
Purpose: Langerhans Cell Histiocytosis (LCH) is a neoplastic disorder characterized by tissue accumulating CD1a(+) histiocytes which frequently carry somatic mutations. Irrespective of mutation status, these LCH-cells display constitutively active kinases belonging to the MAPK pathway. We evaluated,...
Autores principales: | , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Taylor & Francis
2015
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5323006/ https://www.ncbi.nlm.nih.gov/pubmed/28255525 http://dx.doi.org/10.1080/2162402X.2015.1084463 |
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author | Quispel, Willemijn T. Stegehuis-Kamp, Janine A. Blijleven, Laura Santos, Susy J. Lourda, Magda van den Bos, Cor van Halteren, Astrid G.S. Egeler, R. Maarten |
author_facet | Quispel, Willemijn T. Stegehuis-Kamp, Janine A. Blijleven, Laura Santos, Susy J. Lourda, Magda van den Bos, Cor van Halteren, Astrid G.S. Egeler, R. Maarten |
author_sort | Quispel, Willemijn T. |
collection | PubMed |
description | Purpose: Langerhans Cell Histiocytosis (LCH) is a neoplastic disorder characterized by tissue accumulating CD1a(+) histiocytes which frequently carry somatic mutations. Irrespective of mutation status, these LCH-cells display constitutively active kinases belonging to the MAPK pathway. We evaluated, in retrospect, the contribution of individual components of the MAPK-activating and chemotaxis-promoting TNF-CXCR4-CXCL12 axis to LCH manifestation and outcome. Experimental design: CXCR4, CXCL12 and TNF protein expression was immunohistochemically analyzed in 70 LCH-affected biopsies. The presence of CXCR4(+)CD1a(+) cells in peripheral blood (PB) and/or bone marrow (BM) samples was evaluated by flowcytometry in 13 therapy-naive LCH-patients. Results: CXCL12 was detected in 68/70 (97%) biopsies. CXCR4(+)LCH-cells were present in 50/70 (71%) biopsies; their presence was associated with higher levels of intralesional TNF. Circulating CD1a(+)CXCR4(+) cells were detected in 4/13 (31%) therapy-naïve LCH-patients which displayed BRAF(V600E) (2/4), MAP2K1 (1/4) or no (1/4) mutations in their tissues. These CD11c co-expressing CD1a(+)CXCR4(+)cells migrated to CXCL12 in chemotaxis assays. Lesional CXCR4(+)LCH-cells were detected in 18/20 cases who presented with LCH manifestation at multiple sites and in 5/23 (22%) patients who developed additional lesions after initially presenting with a single lesion. The CXCR4 status at onset proved to be an independent risk factor for LCH reactivation in multivariate analysis (odds ratio 10.4, p = 0.034). Conclusions: This study provides the first evidence that CXCR4 is involved in the homing and retention of LCH-cells in CXCL12-expressing tissues and qualifies CXCR4 as a candidate prognostic marker for less favorable disease outcome. |
format | Online Article Text |
id | pubmed-5323006 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2015 |
publisher | Taylor & Francis |
record_format | MEDLINE/PubMed |
spelling | pubmed-53230062017-03-02 The presence of CXCR4(+) CD1a(+) cells at onset of Langerhans cell histiocytosis is associated with a less favorable outcome Quispel, Willemijn T. Stegehuis-Kamp, Janine A. Blijleven, Laura Santos, Susy J. Lourda, Magda van den Bos, Cor van Halteren, Astrid G.S. Egeler, R. Maarten Oncoimmunology Original Research Purpose: Langerhans Cell Histiocytosis (LCH) is a neoplastic disorder characterized by tissue accumulating CD1a(+) histiocytes which frequently carry somatic mutations. Irrespective of mutation status, these LCH-cells display constitutively active kinases belonging to the MAPK pathway. We evaluated, in retrospect, the contribution of individual components of the MAPK-activating and chemotaxis-promoting TNF-CXCR4-CXCL12 axis to LCH manifestation and outcome. Experimental design: CXCR4, CXCL12 and TNF protein expression was immunohistochemically analyzed in 70 LCH-affected biopsies. The presence of CXCR4(+)CD1a(+) cells in peripheral blood (PB) and/or bone marrow (BM) samples was evaluated by flowcytometry in 13 therapy-naive LCH-patients. Results: CXCL12 was detected in 68/70 (97%) biopsies. CXCR4(+)LCH-cells were present in 50/70 (71%) biopsies; their presence was associated with higher levels of intralesional TNF. Circulating CD1a(+)CXCR4(+) cells were detected in 4/13 (31%) therapy-naïve LCH-patients which displayed BRAF(V600E) (2/4), MAP2K1 (1/4) or no (1/4) mutations in their tissues. These CD11c co-expressing CD1a(+)CXCR4(+)cells migrated to CXCL12 in chemotaxis assays. Lesional CXCR4(+)LCH-cells were detected in 18/20 cases who presented with LCH manifestation at multiple sites and in 5/23 (22%) patients who developed additional lesions after initially presenting with a single lesion. The CXCR4 status at onset proved to be an independent risk factor for LCH reactivation in multivariate analysis (odds ratio 10.4, p = 0.034). Conclusions: This study provides the first evidence that CXCR4 is involved in the homing and retention of LCH-cells in CXCL12-expressing tissues and qualifies CXCR4 as a candidate prognostic marker for less favorable disease outcome. Taylor & Francis 2015-08-31 /pmc/articles/PMC5323006/ /pubmed/28255525 http://dx.doi.org/10.1080/2162402X.2015.1084463 Text en © 2016 The Author(s). Published with license by Taylor & Francis Group, LLC http://creativecommons.org/licenses/by/3.0/ This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. The moral rights of the named author(s) have been asserted. |
spellingShingle | Original Research Quispel, Willemijn T. Stegehuis-Kamp, Janine A. Blijleven, Laura Santos, Susy J. Lourda, Magda van den Bos, Cor van Halteren, Astrid G.S. Egeler, R. Maarten The presence of CXCR4(+) CD1a(+) cells at onset of Langerhans cell histiocytosis is associated with a less favorable outcome |
title | The presence of CXCR4(+) CD1a(+) cells at onset of Langerhans cell histiocytosis is associated with a less favorable outcome |
title_full | The presence of CXCR4(+) CD1a(+) cells at onset of Langerhans cell histiocytosis is associated with a less favorable outcome |
title_fullStr | The presence of CXCR4(+) CD1a(+) cells at onset of Langerhans cell histiocytosis is associated with a less favorable outcome |
title_full_unstemmed | The presence of CXCR4(+) CD1a(+) cells at onset of Langerhans cell histiocytosis is associated with a less favorable outcome |
title_short | The presence of CXCR4(+) CD1a(+) cells at onset of Langerhans cell histiocytosis is associated with a less favorable outcome |
title_sort | presence of cxcr4(+) cd1a(+) cells at onset of langerhans cell histiocytosis is associated with a less favorable outcome |
topic | Original Research |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5323006/ https://www.ncbi.nlm.nih.gov/pubmed/28255525 http://dx.doi.org/10.1080/2162402X.2015.1084463 |
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