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Your search keyword '"Buus, Terkild B."' showing total 2 results
Start Over Author "Buus, Terkild B." Topic cutaneous t cell lymphoma
2 results on '"Buus, Terkild B."'

1. Phenotypic plasticity of malignant T cells in blood and skin of a Sézary syndrome patient revealed by single cell transcriptomics

Author

Peiffer, Lukas, Gambichler, Thilo, Buus, Terkild B., Horny, Kai, Gravemeyer, Jan, Furtmann, Frauke, Spassova, Ivelina, Kubat, Linda, Susok, Laura, Stranzenbach, René, Srinivas, Nalini, Ødum, Niels, and Becker, Jürgen

Subjects
Cancer Research, reactive T cells, Oncology, inflammation, Sézary syndrome, Medizin, scRNAseq, cutaneous T cell lymphoma, malignant T cells
Abstract

BackgroundSézary Syndrome (SS) is an aggressive leukemic variant of cutaneous T-cell lymphomas (CTCL). In SS patients, malignant T cells are circulating through the blood and cause erythroderma.ObjectiveTo compare the transcriptome of single cells in blood and skin samples from a patient with advanced SS.MethodsWe utilized combined single cell RNA and T-cell receptor (TCR) sequencing (scRNA-seq).ResultsWe scrutinized the malignant T cells in blood and skin in an unbiased manner without pre-sorting of cells. We observed different phenotypes of the same monoclonal malignant T-cell population, confirmed by TCR sequencing and inferred copy number variation analysis. Malignant T cells present in the circulating blood expressed genes resembling central memory T cells such as CCR7, IL7R and CD27. In the skin, we detected two major malignant T-cell populations: One subpopulation was closely related to the malignant T cells from the blood, while the other subpopulation expressed genes reminiscent of skin resident effector memory T cells including GZMB and NKG7. Pseudotime analysis indicated crucial transcriptomic changes in the transition of malignant T cells between blood and skin. These changes included the differential regulation of TXNIP, a putative tumor suppressor in CTCL, and the adaptation to the hypoxic conditions in the skin. Tumor cell proliferation in the skin was supported by stimulating interactions between myeloid cells and malignant T cells.ConclusionsUsing scRNA-seq we detected a high degree of functional heterogeneity within the malignant T-cell population in SS and highlighted crucial differences between SS cells in blood and skin.

Published
2023

2. JAK3 Is Expressed in the Nucleus of Malignant T Cells in Cutaneous T Cell Lymphoma (CTCL).

Author

Vadivel, Chella Krishna, Gluud, Maria, Torres-Rusillo, Sara, Boding, Lasse, Willerslev-Olsen, Andreas, Buus, Terkild B., Nielsen, Tea Kirkegaard, Persson, Jenny L., Bonefeld, Charlotte M., Geisler, Carsten, Krejsgaard, Thorbjorn, Fuglsang, Anja T., Odum, Niels, and Woetmann, Anders

Subjects
CELL nuclei, GENE expression, PHOSPHORYLATION, SKIN diseases, T cells, TRANSFERASES, NUCLEAR proteins, SEZARY syndrome, T-cell lymphoma, SIGNAL peptides, IN vitro studies, JANUS kinases
Abstract

Simple Summary: JAK3 plays an important role in the pathogenesis of cutaneous T cell lymphoma. JAK3 belongs to the Janus kinase family of receptor-associated tyrosine kinases located in cytoplasm adjacent to the plasma membrane. In this study, we show that JAK3 can also be ectopically expressed in the nucleus in CTCL cell lines and primary cells from CTCL patients. Importantly, JAK3 interacts with the nuclear protein RNA polymerase II and phosphorylates Histone H3. Thus, our data provide first evidence for nuclear expression of JAK3 and interactions with key nuclear proteins in malignant T cells suggesting a novel non-canonical role in CTCL. Perturbation in JAK-STAT signaling has been reported in the pathogenesis of cutaneous T cell lymphoma (CTCL). JAK3 is predominantly associated with the intra-cytoplasmic part of IL-2Rγc located in the plasma membrane of hematopoietic cells. Here we demonstrate that JAK3 is also ectopically expressed in the nucleus of malignant T cells. We detected nuclear JAK3 in various CTCL cell lines and primary malignant T cells from patients with Sézary syndrome, a leukemic variant of CTCL. Nuclear localization of JAK3 was independent of its kinase activity whereas STAT3 had a modest effect on nuclear JAK3 expression. Moreover, JAK3 nuclear localization was only weakly affected by blockage of nuclear export. An inhibitor of the nuclear export protein CRM1, Leptomycin B, induced an increased expression of SOCS3 in the nucleus, but only a weak increase in nuclear JAK3. Importantly, immunoprecipitation experiments indicated that JAK3 interacts with the nuclear protein POLR2A, the catalytic subunit of RNA Polymerase II. Kinase assays showed tyrosine phosphorylation of recombinant human Histone H3 by JAK3 in vitro—an effect which was blocked by the JAK inhibitor (Tofacitinib citrate). In conclusion, we provide the first evidence of nuclear localization of JAK3 in malignant T cells. Our findings suggest that JAK3 may have a cytokine-receptor independent function in the nucleus of malignant T cells, and thus a novel non-canonical role in CTCL. [ABSTRACT FROM AUTHOR]

Published
2021
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