Analysis of CTCL cell lines reveals important differences between mycosis fungoides/Sézary syndrome vs. HTLV-1+ leukemic cell lines
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Elena Netchiporouk1,*, Jennifer Gantchev1,*, Matthew Tsang2, Philippe Thibault3, Andrew K. Watters4, John-Douglas Matthew Hughes2, Feras M. Ghazawi2, Anders Woetmann5, Niels Ødum5, Denis Sasseville1 and Ivan V. Litvinov1,2
1Division of Dermatology, McGill University, Montréal, Québec, Canada
2Division of Dermatology, University of Ottawa, Ottawa, Ontario, Canada
3Université de Sherbrooke Rnomics Platform, Sherbrooke, Québec, Canada
4Department of Pathology, McGill University Health Centre, Montreal, Québec, Canada
5Department of International Health, Immunology, and Microbiology, University of Copenhagen, Copenhagen, Denmark
*These authors have contributed equally to this work
Ivan V. Litvinov, email: firstname.lastname@example.org
Denis Sasseville, email: email@example.com
Keywords: human T-cell lymphotropic virus type 1; cutaneous T-cell lymphomas; spectral karyotyping; gene expression analysis; xenograft tumors
Received: July 20, 2017 Accepted: August 26, 2017 Published: October 07, 2017
HTLV-1 is estimated to affect ~20 million people worldwide and in ~5% of carriers it produces Adult T-Cell Leukemia/Lymphoma (ATLL), which can often masquerade and present with classic erythematous pruritic patches and plaques that are typically seen in Mycosis Fungoides (MF) and Sézary Syndrome (SS), the most recognized variants of Cutaneous T-Cell Lymphomas (CTCL). For many years the role of HTLV-1 in the pathogenesis of MF/SS has been hotly debated. In this study we analyzed CTCL vs. HTLV-1+ leukemic cells. We performed G-banding/spectral karyotyping, extensive gene expression analysis, TP53 sequencing in the 11 patient-derived HTLV-1+ (MJ and Hut102) vs. HTLV-1- (Myla, Mac2a, PB2B, HH, H9, Hut78, SZ4, Sez4 and SeAx) CTCL cell lines. We further tested drug sensitivities to commonly used CTCL therapies and studied the ability of these cells to produce subcutaneous xenograft tumors in NOD.Cg-Prkdcscid Il2rgtm1Wjl/SzJ mice. Our work demonstrates that unlike classic advanced MF/SS cells that acquire many ongoing balanced and unbalanced chromosomal translocations, HTLV-1+ CTCL leukemia cells are diploid and exhibit only a minimal number of non-specific chromosomal alterations. Our results indicate that HTLV-1 virus is likely not involved in the pathogenesis of classic MF/SS since it drives a very different pathway of lymphomagenesis based on our findings in these cells. This study also provides for the first time a comprehensive characterization of the CTCL cells with respect to gene expression profiling, TP53 mutation status, ability to produce tumors in mice and response to commonly used therapies.
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