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Blood transcriptional profiling reveals IL-1 and integrin signaling pathways associated with clinical response to extracorporeal photopheresis in patients with leukemic cutaneous T-cell lymphoma

Extracorporeal photopheresis (ECP) is a frontline therapy for patients with leukemic cutaneous T-cell lymphoma (L-CTCL), but its mechanisms of action are not fully understood. This study was to explore the molecular mechanisms underlying clinical response versus non-response in patients with L-CTCL....

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Autores principales: Ying, Zuolin, Shiue, Lisa, Park, Katherine, Kollet, Jutta, Bijani, Pedram, Goswami, Meghali, Duvic, Madeleine, Ni, Xiao
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Impact Journals LLC 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6516711/
https://www.ncbi.nlm.nih.gov/pubmed/31139332
http://dx.doi.org/10.18632/oncotarget.26900
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author Ying, Zuolin
Shiue, Lisa
Park, Katherine
Kollet, Jutta
Bijani, Pedram
Goswami, Meghali
Duvic, Madeleine
Ni, Xiao
author_facet Ying, Zuolin
Shiue, Lisa
Park, Katherine
Kollet, Jutta
Bijani, Pedram
Goswami, Meghali
Duvic, Madeleine
Ni, Xiao
author_sort Ying, Zuolin
collection PubMed
description Extracorporeal photopheresis (ECP) is a frontline therapy for patients with leukemic cutaneous T-cell lymphoma (L-CTCL), but its mechanisms of action are not fully understood. This study was to explore the molecular mechanisms underlying clinical response versus non-response in patients with L-CTCL. We performed blood transcriptional profiling of ten L-CTCL patients at Day 2 and 1 month post- ECP compared to pre-ECP baseline using Agilent Whole Human Genome Microarray technology. Differentially expressed genes (DEGs) between five clinically-responsive patients and five clinically-resistant patients were cross-compared. Higher numbers of genes were modulated in responders than non-responders after ECP at both Day 2 and 1 month, with two thirds of DEGs down-regulated. The down-regulated DEGs at 1 month post-ECP were related to inflammatory, immune and/or stress responses, platelet functions, and chromatin remodeling. Upregulated DEGs were mainly related to functions of the nucleolus. Pathway analysis revealed that integrin and IL-1 signaling pathways were the top pathways affected in responders, which were minimally affected in non-responders. The top upstream transcription regulators affected were IL1B, EGR1, FAS, and TGFB1. Our results suggest that the modulation of cell adhesion and suppression of IL-1β induced inflammation may underlie the efficacy of ECP in L-CTCL.
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spelling pubmed-65167112019-05-28 Blood transcriptional profiling reveals IL-1 and integrin signaling pathways associated with clinical response to extracorporeal photopheresis in patients with leukemic cutaneous T-cell lymphoma Ying, Zuolin Shiue, Lisa Park, Katherine Kollet, Jutta Bijani, Pedram Goswami, Meghali Duvic, Madeleine Ni, Xiao Oncotarget Research Paper Extracorporeal photopheresis (ECP) is a frontline therapy for patients with leukemic cutaneous T-cell lymphoma (L-CTCL), but its mechanisms of action are not fully understood. This study was to explore the molecular mechanisms underlying clinical response versus non-response in patients with L-CTCL. We performed blood transcriptional profiling of ten L-CTCL patients at Day 2 and 1 month post- ECP compared to pre-ECP baseline using Agilent Whole Human Genome Microarray technology. Differentially expressed genes (DEGs) between five clinically-responsive patients and five clinically-resistant patients were cross-compared. Higher numbers of genes were modulated in responders than non-responders after ECP at both Day 2 and 1 month, with two thirds of DEGs down-regulated. The down-regulated DEGs at 1 month post-ECP were related to inflammatory, immune and/or stress responses, platelet functions, and chromatin remodeling. Upregulated DEGs were mainly related to functions of the nucleolus. Pathway analysis revealed that integrin and IL-1 signaling pathways were the top pathways affected in responders, which were minimally affected in non-responders. The top upstream transcription regulators affected were IL1B, EGR1, FAS, and TGFB1. Our results suggest that the modulation of cell adhesion and suppression of IL-1β induced inflammation may underlie the efficacy of ECP in L-CTCL. Impact Journals LLC 2019-05-07 /pmc/articles/PMC6516711/ /pubmed/31139332 http://dx.doi.org/10.18632/oncotarget.26900 Text en http://creativecommons.org/licenses/by/3.0/ Copyright: Ying et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License 3.0 (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
spellingShingle Research Paper
Ying, Zuolin
Shiue, Lisa
Park, Katherine
Kollet, Jutta
Bijani, Pedram
Goswami, Meghali
Duvic, Madeleine
Ni, Xiao
Blood transcriptional profiling reveals IL-1 and integrin signaling pathways associated with clinical response to extracorporeal photopheresis in patients with leukemic cutaneous T-cell lymphoma
title Blood transcriptional profiling reveals IL-1 and integrin signaling pathways associated with clinical response to extracorporeal photopheresis in patients with leukemic cutaneous T-cell lymphoma
title_full Blood transcriptional profiling reveals IL-1 and integrin signaling pathways associated with clinical response to extracorporeal photopheresis in patients with leukemic cutaneous T-cell lymphoma
title_fullStr Blood transcriptional profiling reveals IL-1 and integrin signaling pathways associated with clinical response to extracorporeal photopheresis in patients with leukemic cutaneous T-cell lymphoma
title_full_unstemmed Blood transcriptional profiling reveals IL-1 and integrin signaling pathways associated with clinical response to extracorporeal photopheresis in patients with leukemic cutaneous T-cell lymphoma
title_short Blood transcriptional profiling reveals IL-1 and integrin signaling pathways associated with clinical response to extracorporeal photopheresis in patients with leukemic cutaneous T-cell lymphoma
title_sort blood transcriptional profiling reveals il-1 and integrin signaling pathways associated with clinical response to extracorporeal photopheresis in patients with leukemic cutaneous t-cell lymphoma
topic Research Paper
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6516711/
https://www.ncbi.nlm.nih.gov/pubmed/31139332
http://dx.doi.org/10.18632/oncotarget.26900
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