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Changes in gene expression after epigentic targeted therapy in T-cell prolymphocytic leukemia (T-PLL)

ABSTRACT: Epigenetic therapy overcame alemtuzumab resistance in patients with relapsed T-cell prolymphocytic leukemia and induced the expression of treatment related genes. Method: patient PBMCs from Ficoll, normal patient PBMCS enriched for CD3+/CD8+ or CD3+/CD8+/CD45RA+/CCR7- were extracted in Trizol. Conclusion: Gene expression profiles were changed by epigenetic therapy, likely activating treatment response genes silenced by carcinogenesis.

ORGANISM(S): Homo sapiens

PROVIDER: GSE67368 | GEO | 2015/07/08

SECONDARY ACCESSION(S): PRJNA279603

REPOSITORIES: GEO

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Changes in gene expression after epigentic targeted therapy in T-cell prolymphocytic leukemia (T-PLL)

Project description:Epigenetic therapy overcame alemtuzumab resistance in patients with relapsed T-cell prolymphocytic leukemia and induced the expression of treatment related genes. Method: patient PBMCs from Ficoll, normal patient PBMCS enriched for CD3+/CD8+ or CD3+/CD8+/CD45RA+/CCR7- were extracted in Trizol. Conclusion: Gene expression profiles were changed by epigenetic therapy, likely activating treatment response genes silenced by carcinogenesis. Total RNA from patient Peripheral Blood Mononuclear Cells (PBMC) or from normal negatively enriched CD3+/CD8+/CCR7-/CD45RA+(CD45RO-) blood

2015-07-08 | E-GEOD-67368 | biostudies-arrayexpress

Microarray gene expression analysis of T-cell prolymphocytic leukemia (T-PLL) patient samples

Project description:T-cell prolymphocytic leukemia (T-PLL) is a rare and aggressive neoplasm of mature T-cells with an urgent need for rationally designed therapies to address its notoriously chemo-refractory behavior. To characterize the gene expression profiles, 12 T-PLL MNC samples (>90% tumor cell content) were screened with Illumina gene expression arrays (Human HT‐12 v4 rev.2 Expression Beadchips).

2017-09-08 | E-MTAB-5916 | biostudies-arrayexpress

Genotyping and transcription profiling OF human T-cell prolymphocytic leukemia patients identifies novel chromosomal imbalances AND candidate genes IN T-PLL

Project description:T-cell prolymphocytic leukemia (T-PLL) is a rare aggressive lymphoma derived from mature T cells, which is, in most cases, characterized by the presence of an inv(14)(q11q32)/t(14;14)(q11;q32) and a characteristic pattern of secondary chromosomal aberrations. DNA microarray technology was employed to compare the transcriptomes of eight immunomagnetically purified CD3+ normal donor-derived peripheral blood cell samples, with five highly purified inv(14)/t(14;14)-positive T-PLL blood samples. Between the two experimental groups, 734 genes were identified as differentially expressed, including functionally important genes involved in lymphomagenesis, cell cycle regulation, apoptosis and DNA repair. Notably, the differentially expressed genes were found to be significantly enriched in genomic regions affected by recurrent chromosomal imbalances. Upregulated genes clustered on chromosome arms 6p and 8q, and downregulated genes on 6q, 8p, 10p, 11q and 18p. High-resolution copy-number determination using single nucleotide polymorphism chip technology in 11 inv(14)/t(14;14)-positive T-PLL and 1 without the inv(14) including those analyzed for gene expression, refined chromosomal breakpoints as well as regions of imbalances. In conclusion, combined transcriptional and molecular cytogenetic profiling identified novel specific chromosomal loci and genes that are likely to be involved in disease progression and suggests a gene dosage effect as a pathogenic mechanism in T-PLL. Each Sample has its raw data file linked as a supplementary file. Experiment Overall Design: 12 T-cell prolymphocytic leukaemia samples were hybridized to 50K_Xba SNP arrays.

2008-04-10 | E-GEOD-10387 | biostudies-arrayexpress

ECOG 5998, trial of immunosupressives for the treatment of Large Granular Lymphocyte Leukemia

Project description:Eastern Clinical Oncology Group trial number 5998 determined the efficacy of the immunosupressives methotrexate (step 1) and cylophosphamide (step 2) in the treatment of Large Granular Lymphocyte leukemia. Expression data from pre-treatment samples were evaluated for a priori ability to predict treatment response to Step 1 and for correlation with STAT3 mutation types predictive of response. Method: patient PBMCs from Ficoll, normal patient PBMCS enriched for CD3+/CD8+ or CD3+/CD8+/CD45RA+/CCR7- were extracted in Trizol. Conclusion: A gene expression profile was associated with response to treatment with evidence of particular STAT3 mutations driving this expression profile and response.

2014-12-29 | GSE42664 | GEO

Expression data from T-cell prolymphocytic leukemia (TPLL) and normal T cells

2007-08-27 | GSE5788 | GEO

Transcription profiling of human prolymphocytic leukemina T-cells and normal T-cells

Project description:T-cell prolymphocytic leukemina (T-PLL) is an agressive lymphoma derived from mature T-cells, which is in most cases characterized by the presence of an inv(14)(q11q32) and a characteristic pattern of secondary chromosomal abberations. We used microarrays to compare the transcriptomes of eight immunomagnetically purified CD3+ normal donor derived peripheral blood cells with five highly purified inv(14)-positive T-PLL blood samples. Experiment Overall Design: Purified T-PLL cells and normal T-cells were analyzed on microarrays to identify differentially expressed genes. High-resolution copy number determination using SNP-chip technology and FISH in twelve inv(14)-positive T-PLL showed that differentially expressed genes clustered significantly in regions affectd by recurrent chromosomal imbalances.

2008-12-10 | E-GEOD-5788 | biostudies-arrayexpress

RNA-Seq of T cells sorted from human PBMCs, or from T cells stimulated with CD3/CD28 beads for 4 days, or from the spleen of NSG or NSG-HLA-A2/HHD mice, 7 days after transplantation with human PBMCs

Project description:The goal of the experiment is to describe the overall transcriptomic alterations and signaling pathways activated by T cells upon transplantation in NSG or NSG-HLA-A2/HHD mice. PBMCs and CD3/CD28 activated T cells serve as negative and positive controls of these pathways activation, respectively. PBMCs from 4 different healthy volunteer donors were used. PBMCs from each donor were either used to sort T cells (by FACS) immediately after Ficoll isolation, or immediately stimulated in vitro or injected into mice.

2018-08-14 | E-MTAB-6865 | biostudies-arrayexpress

Characteristics, outcomes, prognostic factors and treatment of patients with T-cell prolymphocytic leukemia (T-PLL).

Project description: Not available

| S-EPMC5834082 | biostudies-other

mRNA profile of CD8 T cells from chronic HBV patients

Project description:The low frequency of HBV-specific CD8+ T cells in the peripheral blood of CHB patients has limited studies of the mechanisms underlying HBV-induced T cell exhaustion. Similar to the expansion defect displayed in HBV-specific CD8+ T cells, TCR-induced proliferation of global CD8+ T cells is impaired in a fraction of chronic HBV (CHB) patients. Thus, examining the molecular regulation of global CD8+ T cell function in CHB patients may provide insight into the exhaustion of HBV-specific CD8+ T cells. We used microarrays to detail the global programme of gene expression of CD8 T cells from CHB patients who have not received anti-viral treatment. Fifteen milliliters of blood was drawn from eachof three CHB patients and three healthy donors. PBMCs were enriched using Ficoll, and CD8+ T cells were purified using positive selection beads to a purity of >95% (Miltenyi Biotec, Auburn, CA). Total RNA was extracted using a mirVana isolation kit (Life Technologies, Carlsbad, CA).

2016-07-01 | E-GEOD-51489 | biostudies-arrayexpress

Histone modification profiling of T-cell prolymphocytic leukemia through chromatin immunoprecipitation and sequencing

Project description:T-cell prolymphocytic leukemia (T-PLL) is a rare disease with rapid clinical course. Whole-exome and whole-genome sequencing have identified structural alterations in T-PLL, including inversion, translocation and copy number variation. Epigenetic alterations are the hallmark of many cancers. However, genome-wide epigenomic profiles have not been reported in T-PLL. In this study, we generated genome-wide maps of regulatory regions in both T-PLL patients and healthy individuals using H3K4me3 and H3K27ac ChIP-seq. We revealed a global alteration of both promoter and enhancer landscape in T-PLL, which supported the role of epigenetic regulation in transcriptional dysregulation of oncogenes and genes involved in DNA damage response and T-cell activation.

2021-04-20 | GSE143374 | GEO

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