Ren, Jingjing, Qu, Rihao, Rahman, Nur Taz, Lewis, Julia M., Ong King, Amber Loren, Liao, Xiaofeng, Mirza, Fatima N., Carlson, Kacie R., Huang, Yaqing, Gigante, Scott, Evans, Benjamin
ORCID: https://orcid.org/0000-0001-6849-9758, Rajendran, Barani Kumar, Xu, Suzanne, Wang, Guilin, Foss, Francine M., Damsky, William, Kluger, Yuval, Krishnaswamy, Smita and Girardi, Michael
(2023)
Integrated transcriptome and trajectory analysis of cutaneous T-cell lymphoma identifies putative precancer populations.
Blood Advances, 7 (3).
pp. 445-457.
ISSN 2473-9529
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Abstract
The incidence of cutaneous T-cell lymphoma (CTCL) increases with age, and blood involvement portends a worse prognosis. To advance our understanding of the development of CTCL and identify potential therapeutic targets, we performed integrative analyses of paired single-cell RNA and T-cell receptor (TCR) sequencing of peripheral blood CD4+ T cells from patients with CTCL to reveal disease-unifying features. The malignant CD4+ T cells of CTCL showed highly diverse transcriptomic profiles across patients, with most displaying a mature Th2 differentiation and T-cell exhaustion phenotype. TCR-CDR3 peptide prediction analysis suggested limited diversity between CTCL samples, consistent with a role for a common antigenic stimulus. Potential of heat diffusion for affinity-based trajectory embedding transition analysis identified putative precancerous circulating populations characterized by an intermediate stage of gene expression and mutation level between the normal CD4+ T cells and malignant CTCL cells. We further revealed the therapeutic potential of targeting CD82 and JAK that endow the malignant CTCL cells with survival and proliferation advantages.
| Item Type: | Article |
|---|---|
| Additional Information: | Publisher Copyright: © 2023 by The American Society of Hematology. |
| Uncontrolled Keywords: | hematology ,/dk/atira/pure/subjectarea/asjc/2700/2720 |
| Faculty \ School: | Faculty of Medicine and Health Sciences > Norwich Medical School |
| Related URLs: | |
| Depositing User: | LivePure Connector |
| Date Deposited: | 12 Aug 2026 19:17 |
| Last Modified: | 12 Aug 2026 19:17 |
| URI: | https://ueaeprints.uea.ac.uk/id/eprint/104104 |
| DOI: | 10.1182/bloodadvances.2022008168 |
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