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Oncogenic role of miR-155 in anaplastic large cell lymphoma lacking the t(2;5) translocation

Anaplastic large cell lymphoma (ALCL) is a rare, aggressive, non-Hodgkin's lymphoma that is characterized by CD30 expression and disease onset in young patients. About half of ALCL patients bear the t(2;5)(p23;q35) translocation, which results in the formation of the nucleophosmin-anaplastic ly...

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Autores principales: Merkel, Olaf, Hamacher, Frank, Griessl, Robert, Grabner, Lisa, Schiefer, Ana-Iris, Prutsch, Nicole, Baer, Constance, Egger, Gerda, Schlederer, Michaela, Krenn, Peter William, Hartmann, Tanja Nicole, Simonitsch-Klupp, Ingrid, Plass, Christoph, Staber, Philipp Bernhard, Moriggl, Richard, Turner, Suzanne D, Greil, Richard, Kenner, Lukas
Formato: Online Artículo Texto
Lenguaje:English
Publicado: John Wiley & Sons, Ltd 2015
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4557053/
https://www.ncbi.nlm.nih.gov/pubmed/25820993
http://dx.doi.org/10.1002/path.4539
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author Merkel, Olaf
Hamacher, Frank
Griessl, Robert
Grabner, Lisa
Schiefer, Ana-Iris
Prutsch, Nicole
Baer, Constance
Egger, Gerda
Schlederer, Michaela
Krenn, Peter William
Hartmann, Tanja Nicole
Simonitsch-Klupp, Ingrid
Plass, Christoph
Staber, Philipp Bernhard
Moriggl, Richard
Turner, Suzanne D
Greil, Richard
Kenner, Lukas
author_facet Merkel, Olaf
Hamacher, Frank
Griessl, Robert
Grabner, Lisa
Schiefer, Ana-Iris
Prutsch, Nicole
Baer, Constance
Egger, Gerda
Schlederer, Michaela
Krenn, Peter William
Hartmann, Tanja Nicole
Simonitsch-Klupp, Ingrid
Plass, Christoph
Staber, Philipp Bernhard
Moriggl, Richard
Turner, Suzanne D
Greil, Richard
Kenner, Lukas
author_sort Merkel, Olaf
collection PubMed
description Anaplastic large cell lymphoma (ALCL) is a rare, aggressive, non-Hodgkin's lymphoma that is characterized by CD30 expression and disease onset in young patients. About half of ALCL patients bear the t(2;5)(p23;q35) translocation, which results in the formation of the nucleophosmin-anaplastic lymphoma tyrosine kinase (NPM–ALK) fusion protein (ALCL ALK(+)). However, little is known about the molecular features and tumour drivers in ALK-negative ALCL (ALCL ALK(−)), which is characterized by a worse prognosis. We found that ALCL ALK(−), in contrast to ALCL ALK(+), lymphomas display high miR-155 expression. Consistent with this, we observed an inverse correlation between miR-155 promoter methylation and miR-155 expression in ALCL. However, no direct effect of the ALK kinase on miR-155 levels was observed. Ago2 immunoprecipitation revealed miR-155 as the most abundant miRNA, and enrichment of target mRNAs C/EBPβ and SOCS1. To investigate its function, we over-expressed miR-155 in ALCL ALK(+) cell lines and demonstrated reduced levels of C/EBPβ and SOCS1. In murine engraftment models of ALCL ALK(−), we showed that anti-miR-155 mimics are able to reduce tumour growth. This goes hand-in-hand with increased levels of cleaved caspase-3 and high SOCS1 in these tumours, which leads to suppression of STAT3 signalling. Moreover, miR-155 induces IL-22 expression and suppresses the C/EBPβ target IL-8. These data suggest that miR-155 can act as a tumour driver in ALCL ALK(−) and blocking miR-155 could be therapeutically relevant. Original miRNA array data are to be found in the supplementary material (Table S1). © 2015 The Authors. The Journal of Pathology published by John Wiley & Sons Ltd on behalf of Pathological Society of Great Britain and Ireland.
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spelling pubmed-45570532015-09-08 Oncogenic role of miR-155 in anaplastic large cell lymphoma lacking the t(2;5) translocation Merkel, Olaf Hamacher, Frank Griessl, Robert Grabner, Lisa Schiefer, Ana-Iris Prutsch, Nicole Baer, Constance Egger, Gerda Schlederer, Michaela Krenn, Peter William Hartmann, Tanja Nicole Simonitsch-Klupp, Ingrid Plass, Christoph Staber, Philipp Bernhard Moriggl, Richard Turner, Suzanne D Greil, Richard Kenner, Lukas J Pathol Original Papers Anaplastic large cell lymphoma (ALCL) is a rare, aggressive, non-Hodgkin's lymphoma that is characterized by CD30 expression and disease onset in young patients. About half of ALCL patients bear the t(2;5)(p23;q35) translocation, which results in the formation of the nucleophosmin-anaplastic lymphoma tyrosine kinase (NPM–ALK) fusion protein (ALCL ALK(+)). However, little is known about the molecular features and tumour drivers in ALK-negative ALCL (ALCL ALK(−)), which is characterized by a worse prognosis. We found that ALCL ALK(−), in contrast to ALCL ALK(+), lymphomas display high miR-155 expression. Consistent with this, we observed an inverse correlation between miR-155 promoter methylation and miR-155 expression in ALCL. However, no direct effect of the ALK kinase on miR-155 levels was observed. Ago2 immunoprecipitation revealed miR-155 as the most abundant miRNA, and enrichment of target mRNAs C/EBPβ and SOCS1. To investigate its function, we over-expressed miR-155 in ALCL ALK(+) cell lines and demonstrated reduced levels of C/EBPβ and SOCS1. In murine engraftment models of ALCL ALK(−), we showed that anti-miR-155 mimics are able to reduce tumour growth. This goes hand-in-hand with increased levels of cleaved caspase-3 and high SOCS1 in these tumours, which leads to suppression of STAT3 signalling. Moreover, miR-155 induces IL-22 expression and suppresses the C/EBPβ target IL-8. These data suggest that miR-155 can act as a tumour driver in ALCL ALK(−) and blocking miR-155 could be therapeutically relevant. Original miRNA array data are to be found in the supplementary material (Table S1). © 2015 The Authors. The Journal of Pathology published by John Wiley & Sons Ltd on behalf of Pathological Society of Great Britain and Ireland. John Wiley & Sons, Ltd 2015-08 2015-04-27 /pmc/articles/PMC4557053/ /pubmed/25820993 http://dx.doi.org/10.1002/path.4539 Text en © 2015 The Authors. The Journal of Pathology published by John Wiley & Sons Ltd on behalf of Pathological Society of Great Britain and Ireland http://creativecommons.org/licenses/by/4.0/ This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.
spellingShingle Original Papers
Merkel, Olaf
Hamacher, Frank
Griessl, Robert
Grabner, Lisa
Schiefer, Ana-Iris
Prutsch, Nicole
Baer, Constance
Egger, Gerda
Schlederer, Michaela
Krenn, Peter William
Hartmann, Tanja Nicole
Simonitsch-Klupp, Ingrid
Plass, Christoph
Staber, Philipp Bernhard
Moriggl, Richard
Turner, Suzanne D
Greil, Richard
Kenner, Lukas
Oncogenic role of miR-155 in anaplastic large cell lymphoma lacking the t(2;5) translocation
title Oncogenic role of miR-155 in anaplastic large cell lymphoma lacking the t(2;5) translocation
title_full Oncogenic role of miR-155 in anaplastic large cell lymphoma lacking the t(2;5) translocation
title_fullStr Oncogenic role of miR-155 in anaplastic large cell lymphoma lacking the t(2;5) translocation
title_full_unstemmed Oncogenic role of miR-155 in anaplastic large cell lymphoma lacking the t(2;5) translocation
title_short Oncogenic role of miR-155 in anaplastic large cell lymphoma lacking the t(2;5) translocation
title_sort oncogenic role of mir-155 in anaplastic large cell lymphoma lacking the t(2;5) translocation
topic Original Papers
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4557053/
https://www.ncbi.nlm.nih.gov/pubmed/25820993
http://dx.doi.org/10.1002/path.4539
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