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Transcriptome Signatures of Sezary Cells from Patients and Cultured Hut 78, Hut 102 and Jurkat Cells

ABSTRACT: Comparative transcriptome profiles of patient-derived Sezary cells and cultured Sezary cell line (Hut78) mycosis fungoides cell line (Hut 102) and non-Sezary T cell leukemia cell line (Jurkat) relative to benign CD4+ T cells from individuals with no T cell malignancy. There are three goals. The first and primary goal is to establish a list of genes with differential expression between Sezary cells and the benign CD4+ T cell counter part from individuals without Sezary syndrome. A secondary goal is to examine if these differentially expresses genes in clinical samples of Sezary cells are preserved in Hut78 and Hut102 cells, which are the two most frequently used experimental cell models of Sezary cells in the research community. The third goal is to examine if these Sezary cell specific genes are also present in a non-Sezary T cell malignancy, such as Jurkat cells, which is derived from a non-Sezary cell T cell leukemia patient.

ORGANISM(S): Homo sapiens

PROVIDER: GSE23113 | GEO | 2010/12/31

SECONDARY ACCESSION(S): PRJNA131499

REPOSITORIES: GEO

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Transcriptome Signatures of Sezary Cells from Patients and Cultured Hut 78, Hut 102 and Jurkat Cells

Project description:Comparative transcriptome profiles of patient-derived Sezary cells and cultured Sezary cell line (Hut78) mycosis fungoides cell line (Hut 102) and non-Sezary T cell leukemia cell line (Jurkat) relative to benign CD4+ T cells from individuals with no T cell malignancy. There are three goals. The first and primary goal is to establish a list of genes with differential expression between Sezary cells and the benign CD4+ T cell counter part from individuals without Sezary syndrome. A secondary goal is to examine if these differentially expresses genes in clinical samples of Sezary cells are preserved in Hut78 and Hut102 cells, which are the two most frequently used experimental cell models of Sezary cells in the research community. The third goal is to examine if these Sezary cell specific genes are also present in a non-Sezary T cell malignancy, such as Jurkat cells, which is derived from a non-Sezary cell T cell leukemia patient. Two color experiment, 6 biological replicates (6 unique patients) with Sezary syndrome, 1 Hut78 cell,1 Hut102 cell and 1 Jurkat cell lines as the experimental samples, each compared with a distinct individual with no T cell malignancy of the skin or the blood.

2010-12-31 | E-GEOD-23113 | biostudies-arrayexpress

Transcriptome of SATB1 transduced Hut78 cells

Project description:Hut78 cell line was used as Sezary syndrome cell model. Comparative transcriptome profiles of SATB1 transduced Hut78 cells (Hut78-SATB1) relative to empty MIG vector transduced control Hut78 cells (Hut78-MIG) were analyzed. The primary goal is to establish a list of genes with differential expression between SATB1 transduced Hut78 cells and control Hut78 cells to identify the gene expression regulation effect of SATB1 expression in Sezary cells.

2011-12-01 | GSE24951 | GEO

Transcriptome of SATB1 transduced Hut78 cells

2011-12-01 | E-GEOD-24951 | biostudies-arrayexpress

Gene expression profiling of resting and stimulated CD4+CD45RO+ T cells from Sezary syndrome patients and normal donors

Project description:Sezary syndrome is an aggressive cutaneous T cell lymphoma with pruritic skin inflammation and immune dysfunction, driven by neoplastic, clonal memory T cells in both peripheral blood and skin. To gain insight into how abnormal gene expression in Sezary syndrome promotes T cell dysfunction, lymphoproliferation and transformation, we first compared functional transcriptomic profiles of both resting and activated memory T cells from Sezary syndrome patients and normal donors. To differentiate gene expression associated with malignancy vs. benign inflammation and proliferation, we performed a within-platform meta-analysis of our data for Sezary syndrome and a GEO data set (GSE12079) for lymphocytic variant hypereosinophilic syndrome (L-HES). L-HES is a benign lymphoproliferation of clonal memory T cells that produces skin symptoms very similar to Sezary syndrome. This approach revealed gene expression changes unique to either Sezary syndrome or L-HES, and a subset of genes dysregulated in both SS and L-HES. L-HES patient 1 progressed to peripheral T cell lymphoma, and acquired Sezary-like gene expression during progression, suggesting that these genes contribute to neoplastic transformation.

2019-11-16 | GSE131738 | GEO

Epigenetic inhibitors

Project description:The project aims to looks at differential gene targets in the human Sezary syndrome HuT78 cell line when treated with epigenetic inhibitors romidepsin, F5446, and chaetocin compared to the vehicle treated cells (DMSO) for 72hrs.

2022-10-26 | GSE159963 | GEO

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

Project description:Sezary syndrome (SS) is a rare, aggressive leukemic variant of cutaneous T cell lymphoma (CTCL) that lacks adequate therapeutic options and representative small animal models. Here we demonstrate that IL-15 is a critical CTCL growth and survival factor. Importantly, a genetically engineered immunodeficient mouse model expressing human IL-15 uniquely supported the growth of patient derived Sezary cells relative to conventional immunodeficient mouse strains. Patient derived xenograft (PDX) SS models recapacitated the pathologic features of the human disease, including skin infiltration and spread of leukemic cells to the periphery, and maintained the dependence on human IL-15 upon serial in vivo passaging. Detailed molecular characterization of the engrafted cells by single cell transcriptome analysis revealed tissue specific regulation of gene expression and distinct clonal engraftment patterns. Overall, we document an important dependence of Sezary cell survival and proliferation on IL-15 signaling and the utility of the humanized IL-15, immunodeficient mice for SS PDX model generation. Furthermore, these studies advocate for the thorough molecular understanding of the resultant PDX models to maximize their translational impact.

2023-09-29 | GSE227326 | GEO

Microenvironment-dependent growth of Sezary cells in humanized IL-15 mice [scRNA/TCR-seq]

2023-09-29 | GSE229406 | GEO

Genomic Analysis of Mycosis Fungoides and Sézary Syndrome

Project description:<p>Mycosis Fungoides (MF) and Sézary Syndrome (Sz) comprise the majority of Cutaneous T-Cell Lymphoma (CTCL) cases and are characterized by clinical heterogeneity. This array of symptoms includes skin patches, plaques and tumors as well as blood involvement and erythroderma. Because the genetic basis of CTCL is still poorly understood, we performed whole-exome sequencing on 11 MF/Sz samples and their matched, normal control DNA. Upon analyzing this data, we distilled a list of an additional 494 genes to be sequenced at depth. The majority of these 494 genes were sequenced in the exons alone, however, for a small subset of these genes we sequenced the entire genomic locus in search of structural variation events. This 494 gene targeted resequencing effort was performed upon 72 patients with MF/Sz and their matched, normal control DNA. An additional 5 MF/Sz and matched, normal DNA samples underwent whole genome amplification (WGA) prior to library preparation, which appears to have introduced mutations into these samples, however we also include them here. We additionally include 10 MF/Sz samples without a matched, normal control samples, 1 of which underwent WGA. In addition to primary disease samples, we also performed targeted resequencing on 4 CTCL cell lines (HH, MyLa, SeAx and Hut78) as well as on H9 cells (a subclone of Hut78 cells) and Jurkat cells, a T-ALL derived cell line that was used as an experimental system for our work. In sum, this data deposition includes exome and/or targeted resequencing from 92 individuals with 192 samples submitted.</p>

| phs000913 | dbGaP

Integrated Genomic Analysis of Sezary Syndrome

Project description:Integrated Genomic Analysis of Sezary Syndrome

| PRJNA272829 | ENA

Methyltransferase Inhibitors Restore SATB1 Protective Activity Against Cutaneous T cell Lymphoma

Project description:We report Chromatin Immunoprecipitation for the histone modifications H3K27ac, H3K27m3 and H3K9m3 in human leukemia and lymphoma cell lines HuT78, Jurkat, K562, and RAJI to ascertain the regulatory landscape of in regards to transcriptional repression and activation.

2022-10-26 | GSE159962 | GEO

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