Oncotarget

Research Papers:

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

Zuolin Ying, Lisa Shiue, Katherine Park, Jutta Kollet, Pedram Bijani, Meghali Goswami, Madeleine Duvic and Xiao Ni

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Oncotarget. 2019; 10:3183-3197. https://doi.org/10.18632/oncotarget.26900

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Abstract

Zuolin Ying1, Lisa Shiue1, Katherine Park1, Jutta Kollet2, Pedram Bijani1, Meghali Goswami1, Madeleine Duvic1 and Xiao Ni1

1 Department of Dermatology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA

2 Bioinformatics, Miltenyi Biotec GmbH, Beigisch Gladbach, 51429, Germany

Correspondence to:

Xiao Ni,email: xiaoni@mdanderson.org

Keywords: non-Hodgkin’s lymphoma; cutaneous T-cell lymphoma; extracorporeal photopheresis; microarray; integrin

Received: March 01, 2019     Accepted: April 14, 2019     Published: May 07, 2019

ABSTRACT

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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