Analysis of CTCL cell lines reveals important differences between mycosis fungoides/Sézary syndrome <i>vs. HTLV-1+</i> leukemic cell lines
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Bibliographic record
Abstract
// Elena Netchiporouk 1, * , Jennifer Gantchev 1, * , Matthew Tsang 2 , Philippe Thibault 3 , Andrew K. Watters 4 , John-Douglas Matthew Hughes 2 , Feras M. Ghazawi 2 , Anders Woetmann 5 , Niels Ødum 5 , Denis Sasseville 1 and Ivan V. Litvinov 1, 2 1 Division of Dermatology, McGill University, Montréal, Québec, Canada 2 Division of Dermatology, University of Ottawa, Ottawa, Ontario, Canada 3 Université de Sherbrooke Rnomics Platform, Sherbrooke, Québec, Canada 4 Department of Pathology, McGill University Health Centre, Montreal, Québec, Canada 5 Department of International Health, Immunology, and Microbiology, University of Copenhagen, Copenhagen, Denmark * These authors have contributed equally to this work Correspondence to: Ivan V. Litvinov, email: ivan.litvinov@mcgill.ca Denis Sasseville, email: denis.sasseville@mcgill.ca 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 ABSTRACT 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-Prkdc scid Il2rg tm1Wjl /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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Full frame distilled prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. Learned from the 10,348 direct Codex labels and 10,348 direct Gemma labels. Candidate is the union of thresholded teacher heads; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels or direct frontier model labels.
Codex and Gemma teacher scores by category
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.000 | 0.000 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.002 | 0.001 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.001 | 0.001 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.001 | 0.000 |
| Research integrity | 0.000 | 0.000 |
| Insufficient payload (model declined to judge) | 0.000 | 0.000 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from it