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Macrophage-mediated chronic lymphocytic leukemia cell survival is independent of APRIL signaling
Survival of chronic lymphocytic leukemia (CLL) cells is mainly driven by interactions within the lymph node (LN) microenvironment with bystander cells such as T cells or cells from the monocytic lineage. Although the survival effect by T cells is largely governed by the TNFR ligand family member CD4...
Autores principales: | , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Nature Publishing Group
2016
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4979474/ https://www.ncbi.nlm.nih.gov/pubmed/27551513 http://dx.doi.org/10.1038/cddiscovery.2016.20 |
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author | van Attekum, MHA Terpstra, S Reinen, E Kater, AP Eldering, E |
author_facet | van Attekum, MHA Terpstra, S Reinen, E Kater, AP Eldering, E |
author_sort | van Attekum, MHA |
collection | PubMed |
description | Survival of chronic lymphocytic leukemia (CLL) cells is mainly driven by interactions within the lymph node (LN) microenvironment with bystander cells such as T cells or cells from the monocytic lineage. Although the survival effect by T cells is largely governed by the TNFR ligand family member CD40L, the exact mechanism of monocyte-derived cell-induced survival is not known. An important role has been attributed to the TNFR ligand, a proliferation-inducing ligand (APRIL), although the exact mechanism remained unclear. Since we detected that APRIL was expressed by CD68+ cells in CLL LN, we addressed its relevance in various aspects of CLL biology, using a novel APRIL overexpressing co-culture system, recombinant APRIL, and APRIL reporter cells. Unexpectedly, we found, that in these various systems, APRIL had no effect on survival of CLL cells, and activation of NF-κB was not enhanced on APRIL stimulation. Moreover, APRIL stity mulation did not affect CLL proliferation, neither as single stimulus nor in combination with known CLL proliferation stimuli. Furthermore, the survival effect conveyed by macrophages to CLL cells was not affected by transmembrane activator and CAML interactor-Fc, an APRIL decoy receptor. We conclude that the direct role ascribed to APRIL in CLL cell survival might be overestimated due to application of supraphysiological levels of recombinant APRIL. |
format | Online Article Text |
id | pubmed-4979474 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2016 |
publisher | Nature Publishing Group |
record_format | MEDLINE/PubMed |
spelling | pubmed-49794742016-08-22 Macrophage-mediated chronic lymphocytic leukemia cell survival is independent of APRIL signaling van Attekum, MHA Terpstra, S Reinen, E Kater, AP Eldering, E Cell Death Discov Article Survival of chronic lymphocytic leukemia (CLL) cells is mainly driven by interactions within the lymph node (LN) microenvironment with bystander cells such as T cells or cells from the monocytic lineage. Although the survival effect by T cells is largely governed by the TNFR ligand family member CD40L, the exact mechanism of monocyte-derived cell-induced survival is not known. An important role has been attributed to the TNFR ligand, a proliferation-inducing ligand (APRIL), although the exact mechanism remained unclear. Since we detected that APRIL was expressed by CD68+ cells in CLL LN, we addressed its relevance in various aspects of CLL biology, using a novel APRIL overexpressing co-culture system, recombinant APRIL, and APRIL reporter cells. Unexpectedly, we found, that in these various systems, APRIL had no effect on survival of CLL cells, and activation of NF-κB was not enhanced on APRIL stimulation. Moreover, APRIL stity mulation did not affect CLL proliferation, neither as single stimulus nor in combination with known CLL proliferation stimuli. Furthermore, the survival effect conveyed by macrophages to CLL cells was not affected by transmembrane activator and CAML interactor-Fc, an APRIL decoy receptor. We conclude that the direct role ascribed to APRIL in CLL cell survival might be overestimated due to application of supraphysiological levels of recombinant APRIL. Nature Publishing Group 2016-03-21 /pmc/articles/PMC4979474/ /pubmed/27551513 http://dx.doi.org/10.1038/cddiscovery.2016.20 Text en Copyright © 2016 Cell Death Differentiation Association http://creativecommons.org/licenses/by/4.0/ This work is licensed under a Creative Commons Attribution 4.0 International License. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/ |
spellingShingle | Article van Attekum, MHA Terpstra, S Reinen, E Kater, AP Eldering, E Macrophage-mediated chronic lymphocytic leukemia cell survival is independent of APRIL signaling |
title | Macrophage-mediated chronic lymphocytic leukemia cell survival is independent of APRIL signaling |
title_full | Macrophage-mediated chronic lymphocytic leukemia cell survival is independent of APRIL signaling |
title_fullStr | Macrophage-mediated chronic lymphocytic leukemia cell survival is independent of APRIL signaling |
title_full_unstemmed | Macrophage-mediated chronic lymphocytic leukemia cell survival is independent of APRIL signaling |
title_short | Macrophage-mediated chronic lymphocytic leukemia cell survival is independent of APRIL signaling |
title_sort | macrophage-mediated chronic lymphocytic leukemia cell survival is independent of april signaling |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4979474/ https://www.ncbi.nlm.nih.gov/pubmed/27551513 http://dx.doi.org/10.1038/cddiscovery.2016.20 |
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