TY - JOUR
T1 - 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
AU - Ying, Zuolin
AU - Shiue, Lisa
AU - Park, Katherine
AU - Kollet, Jutta
AU - Bijani, Pedram
AU - Goswami, Meghali
AU - Duvic, Madeleine
AU - Ni, Xiao
N1 - Funding Information:
This work was supported in part by an investigator-initiated research grant from Therakos, Inc. (LS2010-00033111) to XN, by the Shanghai Municipal Education Commission Studying Abroad Fund to ZLY, the CCTS T32 Pre-doctoral Training Program (TL1RR024147 and UL1RR024148) to LHS, and by the Cancer Center Support Grant (P30 CA16672) (MDACC Genomics Core and Flow Cytometry Core). MD is a Blanche Bender Professor of Cancer Research.
Funding Information:
Authors thank Wei Zhang, Ph.D. and Limei Lu, for their technical support of the microarrays. This work was supported in part by an investigator-initiated research grant from Therakos, Inc. (LS2010-00033111) to XN, by the Shanghai Municipal Education Commission Studying Abroad Fund to ZLY, the CCTS T32 Pre-doctoral Training Program (TL1RR024147 and UL1RR024148) to LHS, and by the Cancer Center Support Grant (P30 CA16672) (MDACC Genomics Core and Flow Cytometry Core). MD is a Blanche Bender Professor of Cancer Research.
Publisher Copyright:
© 2019 Impact Journals LLC. All rights reserved.
PY - 2019/5/1
Y1 - 2019/5/1
N2 - 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.
AB - 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.
KW - Cutaneous T-cell lymphoma
KW - Extracorporeal photopheresis
KW - Integrin
KW - Microarray
KW - Non-Hodgkin’s lymphoma
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U2 - https://doi.org/10.18632/oncotarget.26900
DO - https://doi.org/10.18632/oncotarget.26900
M3 - Article
C2 - 31139332
AN - SCOPUS:85065837291
SN - 1949-2553
VL - 10
SP - 3183
EP - 3197
JO - Oncotarget
JF - Oncotarget
IS - 34
ER -