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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

RNA-seq analysis of differentially expressed genes between primary cells and recurrent cells in a B-prolymphocytic leukemia (B-PLL).

Project description:We confirmed that transcription of FAS was upregulated about 30 fold highly in the recurrent cells that lost CD20 expression and showed tumor lysis syndrome compared to the cells at diagnosis in a B-prolymphocytic leukemia patient.

2024-12-31 | GSE157590 | 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

Tra2b's Ultraconserved Poison Exon relays TCR stimulation to shape T cell fate [ASO_RNASeq]

Project description:Analysis of transcript changes with enough depth for evaluation of splicing changes between CD8+ T cells from human donor PBMCs receiving no stimulation,CD3/CD28 stimulation plus scrambled ASO, or CD3/CD28 plus Tra2b-PE ASO

2024-06-01 | GSE267586 | GEO

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:T-cell prolymphocytic leukemia (T-PLL) is a rare and aggressive disease. In this study, we report our experience from 119 patients with T-PLL.We reviewed the clinico-pathologic records of 119 consecutive patients with T-PLL, who presented to our institution between 1990 and 2016.One hundred and nineteen patients with T-PLL were analysed. Complex karyotype and aberrations in chromosome 14 were seen in 65% and 52% patients, respectively. Seventy-five patients (63%) were previously untreated and 43 (37%) were initially treated outside our institution. Sixty-three previously untreated patients (84%) received frontline therapies. Overall, 95 patients (80%) have died. Median overall survival (OS) from diagnosis was 19?months [95% confidence interval (CI) 16-26?months]. Using recursive partitioning (RP), we found that patients with hemoglobin?<?9.3?g/dl, lactate dehydrogenase (LDH)???1668?IU/l, white blood cell ???208 K/l and ?2M???8?mg/l had significantly inferior OS and patients with hemoglobin?<?9.3?g/dl had inferior progression-free survival (PFS). In multivariate analysis, we identified that presence of pleural effusion [hazard ratio (HR) 2.08 (95% CI 1.11-3.9); P?=?0.02], high LDH (??1668?IU/l) [HR 2.5 (95% CI 1.20-4.24); P?<?0.001)], and low hemoglobin (<?9.3?g/dl) [HR 0.33 (95% CI 0.14-0.75); P?=?0.008] were associated with shorter OS. Fifty-five previously untreated patients received treatment with an alemtuzumab-based regimen (42 monotherapy and 13 combination with pentostatin). Overall response rate, complete remission rate (CR) for single-agent alemtuzumab and alemtuzumab combined with pentostatin were 83%, 66% and 82%, 73% respectively. In patients who achieved initial CR, stem cell transplantation was not associated with longer PFS and OS.Outcomes in T-PLL remain poor. Multicenter collaborative effort is required to conduct prospective studies.

| S-EPMC5834082 | biostudies-other

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