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Transcription profiling of human T cells from patients presenting with AML compared with healthy T cells

ABSTRACT: Work previously published by our group has demonstrated that T cells from patients with chronic lymphocytic leukaemia (CLL) show differentially regulated genes compared with healthy T cells. This study was initiated to examine if these gene expression changes were unique to CLL T cells or common to an alternative leukaemia, acute myeloid leukaemia (AML). Experiment Overall Design: The study was composed of four groups of samples: AML CD4 (n=10), AML CD8 (n=10), Healthy CD4 (n=10), Healthy CD8 (n=11). AML samples were chosen to represent the range of FAB types, prognostic groups and patient outcomes. Healthy T cells were obtained from volunteers. The purity of isolated T cell fractions was greater than 70% in all cases.

ORGANISM(S): Homo sapiens

SUBMITTER: Rifca Le Dieu

PROVIDER: E-GEOD-14924 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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Peripheral blood T cells in acute myeloid leukemia (AML) patients at diagnosis have abnormal phenotype and genotype and form defective immune synapses with AML blasts.

Le Dieu Rifca R Taussig David C DC Ramsay Alan G AG Mitter Richard R Miraki-Moud Faridah F Fatah Rewas R Lee Abigail M AM Lister T Andrew TA Gribben John G JG

Blood 20090826 18

Understanding how the immune system in patients with cancer interacts with malignant cells is critical for the development of successful immunotherapeutic strategies. We studied peripheral blood from newly diagnosed patients with acute myeloid leukemia (AML) to assess the impact of this disease on the patients' T cells. The absolute number of peripheral blood T cells is increased in AML compared with healthy controls. An increase in the absolute number of CD3+56+ cells was also noted. Gene expre ...[more]

PMID: 19710498

Similar Datasets

Characterisation of gene expression changes in T cells from patients presenting with AML compared with healthy T cells

Project description:Work previously published by our group has demonstrated that T cells from patients with chronic lymphocytic leukaemia (CLL) show differentially regulated genes compared with healthy T cells. This study was initiated to examine if these gene expression changes were unique to CLL T cells or common to an alternative leukaemia, acute myeloid leukaemia (AML). Keywords: Comparison of immune cells in health and disease

2009-05-20 | GSE14924 | GEO

Transcription profiling of human CD4 and CD8 T cells to identify effects of cell selection on gene expression

Project description:Negative immunomagnetic selection has become the method of choice for isolating T cell subsets for functional studies due to concerns that directly binding antibody to the surface of a cell, as occurs with positive selection, results in cross-linking of surface antigens, altered gene transcription and subsequent cellular activation. However there is little data to support this. We therefore examined the impact of the method of immunomagnetic cell selection on the gene expression profile of healthy human CD4 and CD8 T cells in a total of 21 cases. Experiment Overall Design: This study was composed of 4 groups of samples: CD4 Negative Selection (n=5), CD4 Positive Selection (n=5), CD8 Negative Selection (n=5), CD8 Positive Selection (n=6). Two samples (PS6 CD8 and PS9 CD4) were removed from the analysis due to discrepant normalised unscaled standard errors

2009-06-01 | E-GEOD-14926 | biostudies-arrayexpress

Expression data from Human CD40L+ Tcells

Project description:To assess the nature of CD8+CD40L+ memory Tcells, we compared the gene expression to CD8+CD40L- and CD4+ counterparts, and found similarities in expression of genes encoding cytokines PBMCs were isolated from five healthy donors. The cells were stimulated with PMA/Ionomycin for 6 h, and subsequently sorted into the CD4+CD45RA-CD40L+, CD8+CD45RA-CD40L-, CD8+CD45RA-CD40L+ populations by FACS-sort

2013-08-05 | E-GEOD-44126 | biostudies-arrayexpress

Transcription profiling of human CD4 T cells and CD8 T cells were obtained from peripheral blood mononuclear cells of previously untreated patients with CLL and healthy individuals reveals chronic lymphocytic leukemia cells induce changes in gene expression of CD4 and CD8 T cells.

Project description:To examine the impact of tumors on the immune system, we compared global gene expression profiles of peripheral blood T cells from previously untreated patients with B cell chronic lymphocytic leukemia (CLL) with those from age-matched healthy donors. Although the cells analyzed were not part of the malignant clone, analysis revealed differentially expressed genes, mainly involved in cell differentiation in CD4 cells and defects in cytoskeleton formation, vesicle trafficking, and cytotoxicity in CD8 cells of the CLL patients. In coculture experiments using CLL cells and T cells from healthy allogeneic donors, similar defects developed in both CD4 and CD8 cells. These changes were induced only with direct contact and were not cytokine mediated. Identification of the specific pathways perturbed in the T cells of cancer-bearing patients will allow us to assess steps to repair these defects, which will likely be required to enhance antitumor immunity. Gene expression profiling was performed to determine whether CLL cells induce changes in T cells in patients with CLL. Experiment Overall Design: CD4 T cells and CD8 T cells were obtained from peripheral blood mononuclear cells of previously untreated patients with CLL and healthy individuals. Gene expression profiling was performed using total RNA and the data were analysed to compare gene expression profile of T cells from patients with CLL to healthy individuals .

2008-06-16 | E-GEOD-8835 | biostudies-arrayexpress

Transcription profiling of mouse model of CLL in Em-TCL1 mice provides a biologically relevant model to unravel and reverse immune deficiency in human cancer.

Project description:Immune deficiency is common in cancer, but the biological basis for this and ways to reverse it remains elusive. Here we present a mouse model of B cell chronic lymphocytic leukemia (CLL) that recapitulates changes in the non-malignant circulating T cells seen in patients with this illness.1 To validate this model, we examined changes in T cell gene expression, protein expression and function in Em-TCL1 transgenic mice as they developed CLL 2,3 and demonstrate that development of CLL in these transgenic mice is associated with changes in impaired T cell function and in gene expression in CD4 and CD8 T cells similar to those observed in patients with this disease. Infusion of CLL cells into non-leukemia bearing Em-TCL1 mice rapidly induces these changes, demonstrating a causal relationship between leukemia and the induction of T cell changes. This model allows dissection of the molecular changes induced in CD4 and CD8 T cells by interaction with leukemia cells and further supports the concept that cancer results in complex abnormalities in the immune microenvironment. Gene expression profiling was performed to determine whether Em-TCL1 murine model of chronic lymphocytic leukemia (CLL) mimics T cell defects induced by CLL cells in patients with CLL. Experiment Overall Design: CD4 T cells and CD8 T cells were obtained from spleens of B6C3 and Em-TCL1 transgenic murine model of CLL or from peripheral blood mononuclear cells of previously untreated patients with CLL and healthy individuals (Pubmed ID: 15965501). Gene expression profiling was performed using total RNA and the data were analysed to compare gene expression profile of CLL to healthy within or between the species.

2008-06-17 | E-GEOD-8836 | biostudies-arrayexpress

Chronic lymphocytic leukemia cells induce changes in gene expression of CD4 and CD8 T cells.

Project description:To examine the impact of tumors on the immune system, we compared global gene expression profiles of peripheral blood T cells from previously untreated patients with B cell chronic lymphocytic leukemia (CLL) with those from age-matched healthy donors. Although the cells analyzed were not part of the malignant clone, analysis revealed differentially expressed genes, mainly involved in cell differentiation in CD4 cells and defects in cytoskeleton formation, vesicle trafficking, and cytotoxicity in CD8 cells of the CLL patients. In coculture experiments using CLL cells and T cells from healthy allogeneic donors, similar defects developed in both CD4 and CD8 cells. These changes were induced only with direct contact and were not cytokine mediated. Identification of the specific pathways perturbed in the T cells of cancer-bearing patients will allow us to assess steps to repair these defects, which will likely be required to enhance antitumor immunity. Gene expression profiling was performed to determine whether CLL cells induce changes in T cells in patients with CLL. Keywords: comparative gene expression profiling analysis.

2007-08-22 | GSE8835 | GEO

Global gene expression profile of primary human leukemic blasts

Project description:The goal of this study is to define the global gene expression profile of primary leukemic blasts from patients with different forms of myeloid leukemia and different FAB subtypes. Here we report the global gene expression profile of 2 patients with AML FAB M5, 2 patients with AML FAB M7, 3 patients with Down syndrome AML FAB M7 and 3 patients with Down syndrome transient leukemia.

2009-12-29 | GSE19681 | GEO

Quantitative Proteomic Profiles of Chronic Lymphocytic Leukaemia <TO BE UPDATED>

Project description:<TO BE UPDATED> Chronic lymphocytic leukaemia (CLL) is a common, adult B-cell leukaemia that has challenges in prognosis and treatment. It is characterised by a heterogeneous clinical course with multiple distinct phenotypes currently defined genetically or with target-specific monoclonal antibodies. While many studies have examined specific protein targets or global mRNA expression in CLL, few have attempted to characterise expression across the whole proteome. To achieve a non-biased, global proteomics characterisation, 14 CLL samples representing the genetic mutant subgroups NOTCH1, SF3B1 and WT, were subjected to quantitative mass spectrometry and compared with normal B cells using two isobaric tag experiments (TMT 10-plex). 6150 proteins were fully quantitated revealing a strong correlation between the regulated proteins across the CLL samples, independent of subtype. >800 proteins demonstrated significant upregulation (p<0.05) across the CLL samples. In addition to several novel cell surface markers, overexpressed proteins were strongly indicative of dysregulation to mRNA processing, spliceosome activity, transcriptional control by RNA pol II and epigenetic mechanisms (all p<10-10). A strong enrichment was observed for proteins coded by chromosome 12, often observed with trisomy in CLL (p<0.001). Downregulated proteins included cell adhesion molecules such as integrins and suggested a reduced capacity for endothelial transmigration (both p<10-10). These findings confirm many previous observations of CLL-specific protein overexpression (eg. CD5, ROR1, matriptase) and identify several novel surface targets for investigation. They also suggest that strong patterns of protein expression exist across CLL subtypes. Together, these results demonstrate the potential of proteomics and advocate the characterisation of further cancer samples by such methods.

2018-01-26 | PXD002004 | Pride

Mapping the HLA ligandome landscape of acute myeloid leukemia: a targeted approach toward peptide-based immunotherapy

Project description:Identification of physiologically relevant peptide vaccine targets calls for the direct analysis of the entirety of naturally presented human leukocyte antigen (HLA) ligands, termed the HLA ligandome. In this study, we implemented this direct approach using immunoprecipitation and mass spectrometry to define acute myeloid leukemia (AML)-associated peptide vaccine targets. Mapping the HLA class I ligandomes of 15 AML patients and 35 healthy controls, more than 25 000 different naturally presented HLA ligands were identified. Target prioritization based on AML exclusivity and high presentation frequency in the AML cohort identified a panel of 132 LiTAAs (ligandome-derived tumor-associated antigens), and 341 corresponding HLA ligands (LiTAPs (ligandome-derived tumor-associated peptides)) represented subset independently in >20% of AML patients. Functional characterization of LiTAPs by interferon-γ ELISPOT (Enzyme-Linked ImmunoSpot) and intracellular cytokine staining confirmed AML-specific CD8+ T-cell recognition. Of note, our platform identified HLA ligands representing several established AML-associated antigens (e.g. NPM1, MAGED1, PRTN3, MPO, WT1), but found 80% of them to be also represented in healthy control samples. Mapping of HLA class II ligandomes provided additional CD4+ T-cell epitopes and potentially synergistic embedded HLA ligands, allowing for complementation of a multipeptide vaccine for the immunotherapy of AML.

2019-10-14 | PXD015748 | Pride

T-Cells from CLL patients

Project description:T cells may have a role in sustaining the leukemic clone in chronic lymphocytic leukemia (CLL). In this study, we have examined the ability of T cells from CLL patients to support the survival of the leukemic B cells in vitro. Additionally, we compared global gene expression of T cells from indolent CLL patients with healthy individuals and multiple myeloma (MM) patients. Apoptosis of purified CLL cells was inhibited in vitro when cocultured with increasing numbers of autologous T cells (p<0.01) but not with normal donors. The anti-apoptotic effect exceeded that of the antiapoptotic cytokine IL-4 (p=0.02) and was greater with CD8+ T cells than with CD4+ cells (p<0.05). The effect depended mainly on cell-cell contact although a significant effect was observed in transwell experiments (p<0.05). Additionally, about 356 genes involved in different cellular pathways were deregulated in T cells of CLL patients compared to healthy individuals and MM patients. The results of gene expression profiling was verified for 7 genes (KLF6, TRAF1, CCL4, CCL5, RANTES, XCL1 and XCL2) using qRT-PCR and immunoblotting. Our results demonstrate that CLL-derived T cells can prevent apoptosis of leukemic cells and have altered expression of genes that may facilitate survival of the leukemic clone. Peripheral blood was collected by venipuncture from CLL patients, multiple myeloma (MM) patients and age-matched healthy individuals with informed consent and approval of the local Ethics Committee in keeping with the Helsinki declaration on the use of human subjects for research.

2011-03-23 | E-GEOD-28107 | biostudies-arrayexpress

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