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CD164 and FCRL3 are highly expressed on CD4+CD26- T cells in Sezary syndrome; inverse correlation between CD164 and CD26 expression

ABSTRACT: Sezary syndrome (SS) represents a leukemic variant of cutaneous T cell lymphoma (CTCL) with circulating malignant CD4 T cells trafficking to the skin. The cell surface molecules present on malignant cells are also expressed on normal CD4 T cells. Therefore, we attempted to find a specific marker for malignant cells that would distinguish them from normal cells. Comprehensive microarray analysis of gene expression in the malignant cells indicated significantly increased levels of mRNA for cell surface markers CD164, a sialomucin found on human CD34+ hematopoietic stem cells, as well as FCRL3, a molecule present on a subset of human natural T regulatory cells. Both markers were increased in CD4 T cells from the SS patients compared to those from Mycosis Fungoides patients and healthy volunteers. Subsequent studies utilizing QPCR and flow cytometry confirmed the increased expression of CD164 and FCRL3 mainly in CD4+CD26- T cells of SS patients. Our results suggest that CD164 can serve as a marker for diagnosis as well as disease monitoring of CTCL/SS, whereas the FCRL3 expression correlates with disease progression.

ORGANISM(S): Homo sapiens

PROVIDER: GSE39041 | GEO | 2019/11/21

REPOSITORIES: GEO

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Transcription profiling of Hut 78 cells (Sezary sndrome) with a stable knockdown of AHI-1 expression to identify mediators of the AHI-1.

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2009-02-21 | E-GEOD-14746 | biostudies-arrayexpress

Microenvironment-dependent growth of Sezary cells in humanized IL-15 mice

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The Mutational Landscape of CTCL and Sezary Syndrome.

Project description:<p>Sezary syndrome is a leukemic and aggressive form of cutaneous T-cell lymphoma (CTCL) resulting from the malignant transformation of skin-homing central memory CD4+ T cells. To identify new genetic alterations involved in Sezary syndrome and CTCL transformation we performed whole-exome sequencing of tumor-normal sample pairs from 26 Sezary syndrome and 16 CTCL patients. These analyses revealed a distinctive pattern of somatic copy number alterations in Sezary syndrome including highly prevalent recurrent chromosomal deletions involving the TP53, RB1, PTEN, DNMT3A, and CDKN1B tumor suppressor genes. Mutation analysis identified a broad spectrum of somatic mutations involving key genes involved in epigenetic regulation (TET2, CREBBP, MLL3, BRD9, SMARCA4 and CHD3) and signaling, including mutations in MAPK1, BRAF, CARD11 and PRKG1 driving increased MAPK, NFKB and NFAT activity upon T-cell receptor stimulation. Collectively, our findings provide new insights into the genetics of Sezary syndrome and CTCL and support the development of personalized therapies targeting key oncogenically activated signaling pathways for the treatment of these diseases.</p>

| phs000994 | dbGaP

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2019-06-25 | GSE124898 | GEO

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2019-03-22 | GSE122703 | GEO

Comprehensive transcriptional and clonotypic analysis of peripheral blood constituents in Sézary syndrome.

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single-cell RNA and TCR sequencing of sorted CD4+CD26- T cells sorted from 7 CTCL peripheral blood samples

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