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Spleen Tyrosine Kinase Is Involved in the CD38 Signal Transduction Pathway in Chronic Lymphocytic Leukemia
The survival and proliferation of CLL cells depends on microenvironmental contacts in lymphoid organs. CD38 is a cell surface receptor that plays an important role in survival and proliferation signaling in CLL. In this study we demonstrate SYK's direct involvement in the CD38 signaling pathway...
Autores principales: | , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Public Library of Science
2016
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5201248/ https://www.ncbi.nlm.nih.gov/pubmed/28036404 http://dx.doi.org/10.1371/journal.pone.0169159 |
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author | Benkisser-Petersen, Marco Buchner, Maike Dörffel, Arlette Dühren-von-Minden, Marcus Claus, Rainer Kläsener, Kathrin Leberecht, Kerstin Burger, Meike Dierks, Christine Jumaa, Hassan Malavasi, Fabio Reth, Michael Veelken, Hendrik Duyster, Justus Zirlik, Katja |
author_facet | Benkisser-Petersen, Marco Buchner, Maike Dörffel, Arlette Dühren-von-Minden, Marcus Claus, Rainer Kläsener, Kathrin Leberecht, Kerstin Burger, Meike Dierks, Christine Jumaa, Hassan Malavasi, Fabio Reth, Michael Veelken, Hendrik Duyster, Justus Zirlik, Katja |
author_sort | Benkisser-Petersen, Marco |
collection | PubMed |
description | The survival and proliferation of CLL cells depends on microenvironmental contacts in lymphoid organs. CD38 is a cell surface receptor that plays an important role in survival and proliferation signaling in CLL. In this study we demonstrate SYK's direct involvement in the CD38 signaling pathway in primary CLL samples. CD38 stimulation of CLL cells revealed SYK activation. SYK downstream target AKT was subsequently induced and MCL-1 expression was increased. Concomitant inhibition of SYK by the SYK inhibitor R406 resulted in reduced activation of AKT and prevented upregulation of MCL-1. Moreover, short-term CD38 stimulation enhanced BCR-signaling, as indicated by increased ERK phosphorylation. CXCL12-dependent migration was increased after CD38 stimulation. Treating CLL cells with R406 inhibited CD38-mediated migration. In addition, we observed marked downregulation of CD38 expression for CLL cells treated with R406 compared to vehicle control. Finally, we observed a clear correlation between CD38 expression on CLL cells and SYK-inhibitor efficacy. In conclusion, our study provides deeper mechanistic insight into the effect of SYK inhibition in CLL. |
format | Online Article Text |
id | pubmed-5201248 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2016 |
publisher | Public Library of Science |
record_format | MEDLINE/PubMed |
spelling | pubmed-52012482017-01-19 Spleen Tyrosine Kinase Is Involved in the CD38 Signal Transduction Pathway in Chronic Lymphocytic Leukemia Benkisser-Petersen, Marco Buchner, Maike Dörffel, Arlette Dühren-von-Minden, Marcus Claus, Rainer Kläsener, Kathrin Leberecht, Kerstin Burger, Meike Dierks, Christine Jumaa, Hassan Malavasi, Fabio Reth, Michael Veelken, Hendrik Duyster, Justus Zirlik, Katja PLoS One Research Article The survival and proliferation of CLL cells depends on microenvironmental contacts in lymphoid organs. CD38 is a cell surface receptor that plays an important role in survival and proliferation signaling in CLL. In this study we demonstrate SYK's direct involvement in the CD38 signaling pathway in primary CLL samples. CD38 stimulation of CLL cells revealed SYK activation. SYK downstream target AKT was subsequently induced and MCL-1 expression was increased. Concomitant inhibition of SYK by the SYK inhibitor R406 resulted in reduced activation of AKT and prevented upregulation of MCL-1. Moreover, short-term CD38 stimulation enhanced BCR-signaling, as indicated by increased ERK phosphorylation. CXCL12-dependent migration was increased after CD38 stimulation. Treating CLL cells with R406 inhibited CD38-mediated migration. In addition, we observed marked downregulation of CD38 expression for CLL cells treated with R406 compared to vehicle control. Finally, we observed a clear correlation between CD38 expression on CLL cells and SYK-inhibitor efficacy. In conclusion, our study provides deeper mechanistic insight into the effect of SYK inhibition in CLL. Public Library of Science 2016-12-30 /pmc/articles/PMC5201248/ /pubmed/28036404 http://dx.doi.org/10.1371/journal.pone.0169159 Text en © 2016 Benkisser-Petersen et al http://creativecommons.org/licenses/by/4.0/ This is an open access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. |
spellingShingle | Research Article Benkisser-Petersen, Marco Buchner, Maike Dörffel, Arlette Dühren-von-Minden, Marcus Claus, Rainer Kläsener, Kathrin Leberecht, Kerstin Burger, Meike Dierks, Christine Jumaa, Hassan Malavasi, Fabio Reth, Michael Veelken, Hendrik Duyster, Justus Zirlik, Katja Spleen Tyrosine Kinase Is Involved in the CD38 Signal Transduction Pathway in Chronic Lymphocytic Leukemia |
title | Spleen Tyrosine Kinase Is Involved in the CD38 Signal Transduction Pathway in Chronic Lymphocytic Leukemia |
title_full | Spleen Tyrosine Kinase Is Involved in the CD38 Signal Transduction Pathway in Chronic Lymphocytic Leukemia |
title_fullStr | Spleen Tyrosine Kinase Is Involved in the CD38 Signal Transduction Pathway in Chronic Lymphocytic Leukemia |
title_full_unstemmed | Spleen Tyrosine Kinase Is Involved in the CD38 Signal Transduction Pathway in Chronic Lymphocytic Leukemia |
title_short | Spleen Tyrosine Kinase Is Involved in the CD38 Signal Transduction Pathway in Chronic Lymphocytic Leukemia |
title_sort | spleen tyrosine kinase is involved in the cd38 signal transduction pathway in chronic lymphocytic leukemia |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5201248/ https://www.ncbi.nlm.nih.gov/pubmed/28036404 http://dx.doi.org/10.1371/journal.pone.0169159 |
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