Journal article
Single-Cell Profiling of Cutaneous T-Cell Lymphoma Reveals Underlying Heterogeneity Associated with Disease Progression
Clinical cancer research, Vol.25(10), pp.2996-3005
05/15/2019
DOI: 10.1158/1078-0432.CCR-18-3309
PMCID: PMC6659117
PMID: 30718356
Abstract
Purpose: Cutaneous T-cell lymphomas (CTCL), encompassing a spectrum of T-cell lymphoproliferative disorders involving the skin, have collectively increased in incidence over the last 40 years. Sezary syndrome is an aggressive form of CTCL characterized by significant presence of malignant cells in both the blood and skin. The guarded prognosis for Sezary syndrome reflects a lack of reliably effective therapy, due, in part, to an incomplete understanding of disease pathogenesis.
Experimental Design: Using single-cell sequencing of RNA and the machine-learning reverse graph embedding approach in the Monocle package, we defined a model featuring distinct transcriptomic states within Sezary syndrome. Gene expression used to differentiate the unique transcriptional states were further used to develop a boosted tree classification for early versus late CTCL disease.
Results: Our analysis showed the involvement of FOXP3(+) malignant T cells during clonal evolution, transitioning from FOXP3(+) T cells to GATA3(+) or IKZF2(+) (HELIOS) tumor cells. Transcriptomic diversities in a clonal tumor can be used to predict disease stage, and we were able to characterize a gene signature that predicts disease stage with close to 80% accuracy. FOXP3 was found to be the most important factor to predict early disease in CTCL, along with another 19 genes used to predict CTCL stage.
Conclusions: This work offers insight into the heterogeneity of Sezary syndrome, providing better understanding of the transcriptomic diversities within a clonal tumor. This transcriptional heterogeneity can predict tumor stage and thereby offer guidance for therapy.
Details
- Title: Subtitle
- Single-Cell Profiling of Cutaneous T-Cell Lymphoma Reveals Underlying Heterogeneity Associated with Disease Progression
- Creators
- Nicholas Borcherding - University of IowaAndrew P. Voigt - University of IowaVincent Liu - Holden Comprehensive Cancer Center, University of Iowa, College of Medicine, Iowa City, Iowa.Brian K. Link - Holden Comprehensive Cancer Center, University of Iowa, College of Medicine, Iowa City, Iowa.Weizhou Zhang - University of IowaAli Jabbari - University of Iowa
- Resource Type
- Journal article
- Publication Details
- Clinical cancer research, Vol.25(10), pp.2996-3005
- Publisher
- Amer Assoc Cancer Research
- DOI
- 10.1158/1078-0432.CCR-18-3309
- PMID
- 30718356
- PMCID
- PMC6659117
- ISSN
- 1078-0432
- eISSN
- 1557-3265
- Number of pages
- 10
- Grant note
- P50CA097274 / NATIONAL CANCER INSTITUTE; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA; NIH National Cancer Institute (NCI) K08AR069111 / NATIONAL INSTITUTE OF ARTHRITIS AND MUSCULOSKELETAL AND SKIN DISEASES; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA; NIH National Institute of Arthritis & Musculoskeletal & Skin Diseases (NIAMS) University of Iowa Carver College of Medicine Iowa City Veteran's Administration Medical Center AR069111 / NIH; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA CA206255 / F30 fellowship Carver College of Medicine, Holden Comprehensive Cancer Center P30CA086862 / Holden Comprehensive Cancer Center (NCI of the NIH) Carver College of Medicine/Holden Comprehensive Cancer Center core research facility at the University of Iowa T32GM007337 / NATIONAL INSTITUTE OF GENERAL MEDICAL SCIENCES; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA; NIH National Institute of General Medical Sciences (NIGMS)
- Language
- English
- Date published
- 05/15/2019
- Academic Unit
- Dermatology; Hematology, Oncology, and Blood & Marrow Transplantation; The University of Iowa Institute for Vision Research; Pathology; Radiation Oncology; Internal Medicine
- Record Identifier
- 9984296311702771
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