Integrated transcriptome and trajectory analysis of cutaneous T-cell lymphoma identifies putative precancer populations

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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, 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
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Depositing User: LivePure Connector
Date Deposited: 12 Aug 2026 19:17
Last Modified: 12 Oct 2026 10:09
URI: https://ueaeprints.uea.ac.uk/id/eprint/104104
DOI: 10.1182/bloodadvances.2022008168

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