ABSTRACT: Whole genome gene expression profiling in CD4+ T-cells, FACS-sorted based on CADM1/CD7 expression levels, in Adult T-cell Leukemia-lymphoma (ATL) patients, HTLV-1 carriers, and in healthy volunteers.
Project description:CADM1 overexpresion and stepwise downregulation of CD7 in CD4+T-cells from ATL patients and HTLV-1 carriers accurately reflect the process of disease, i.e., oligoclonally and clonally exanding cells are accumulated in D (CADM1posCD7dim) and N (CADM1posCD7neg) populations, respectively. Moreover, gene expression profiling of each subpopulation supported that notion. PBMCs of asymptomatic carriers (ACs) and ATLs were subgrouped based on CADM1 and CD7 expression levels by multicolor flow cytometry. FACS-sorted subpopulations were then subjected to extraction of total RNA, followed by Cy-3 labeling and human whole genome gene expression microarray analyses.
Project description:HTLV-1 infected individuals stay as carriers for their lifetimes, while the rest of 5% are killed by ATL. ATL leukemogenesis is a complex process involving accumulation of multiple genetic abnormalities in HTLV-1 infected cells. To clarify genetic events underlying ATL leukemogenesis, we conducted comprehensive miRNA expression profiling in 40 ATL patients and in 22 healthy volunteers. Total RNA samples from PBMC of ATL patients (mostly HTLV-1 inefcted CD4+ T-cells) and from CD4+ T-cells from healthy donors were subjected to Cy-3 labeling followed by miRNA expression microarray analyses.
Project description:HTLV-1 infected individuals stay as carriers for their lifetimes, while the rest of 5% are killed by ATL. ATL leukemogenesis is a complex process involving accumulation of multiple genetic abnormalities in HTLV-1 infected cells. To clarify genetic events underlying ATL leukemogenesis, we conducted comprehensive gene expression profiling in 52 ATL patients and in 21 healthy volunteers. Total RNA samples from PBMC of ATL patients (mostly HTLV-1 inefcted CD4+ T-cells) and from CD4+ T-cells from healthy donors were subjected to Cy-3 labeling followed by human whole genome gene expression microarray analyses.
Project description:HTLV-1 infected individuals stay as carriers for their lifetimes, while the rest of 5% are killed by ATL. ATL leukemogenesis is a complex process involving accumulation of multiple genetic abnormalities in HTLV-1 infected cells. To clarify genetic events underlying ATL leukemogenesis, we conducted comprehensive gene expression profiling in 52 ATL patients and in 21 healthy volunteers.
Project description:HTLV-1 infected individuals stay as carriers for their lifetimes, while the rest of 5% are killed by ATL. ATL leukemogenesis is a complex process involving accumulation of multiple genetic abnormalities in HTLV-1 infected cells. To clarify genetic events underlying ATL leukemogenesis, we conducted comprehensive miRNA expression profiling in 40 ATL patients and in 22 healthy volunteers.
Project description:CADM1 overexpresion and stepwise downregulation of CD7 in CD4+T-cells from ATL patients and HTLV-1 carriers accurately reflect the process of disease, i.e., oligoclonally and clonally exanding cells are accumulated in D (CADM1posCD7dim) and N (CADM1posCD7neg) populations, respectively. Moreover, gene expression profiling of each subpopulation supported that notion.
Project description:We examined the gene expression profiles of CD4+ T-cells isolated from 7 ATL, 12 HAM/TSP and 11 AC (asymptomatic carriers) to identify gene signatures that may be characteristic for these particular diseases. Using gene expression arrays, we identified ~ 1039 immune-related genes that were differentially expressed in CD4+ T cells; using stringent exclusion criteria, a 122 gene signature could be divided into 3 groups: I) ATL-specific; II) common; and III) HAM/TSP-specific markers To better understand the genetic differences between HTLV-1-associated diseases, we examined the gene expression profile of T lymphocytes from patients either suffering from ATL, HAM/TSP or carrying the HTLV-1 virus without any symptoms. Microarray experiments were performed using the human ImmuneArray cDNA array (UHN Microarray Center, University of Toronto). We used the Stratagene Universal Control, labelled Cy5 for all samples in a competitive hybridization.
Project description:Adult T-cell leukemia/lymphoma (ATL) is a malignancy of mature CD4+ T-cells caused by human T-cell lymphotropic virus type 1 (HTLV-1). Recently, it has been noted that some epigenome abnormalities including DNA methylation and tri-methylation at histone H3Lys27 (H3K27me3) contribute to malignant transformation of ATL. Hence, we investigate the combined effect of DNA demethylating agents and enhancer of zeste homolog 2 (EZH2), which catalyze H3K27me3, inhibitors in ATL. Methylaome analyse revealed that OR21 and the combination changes DNA methylation.
Project description:Adult T-cell leukemia/lymphoma (ATL) is a malignancy of mature CD4+ T-cells caused by human T-cell lymphotropic virus type 1 (HTLV-1). Recently, it has been noted that some epigenome abnormalities including DNA methylation and tri-methylation at histone H3Lys27 (H3K27me3) contribute to malignant transformation of ATL. Hence, we investigate the combined effect of DNA demethylating agents and enhancer of zeste homolog 2 (EZH2), which catalyze H3K27me3, inhibitors in ATL. Gene expression microarray analyses revealed that the combination changes gene expressions stronger than the single treatment.
Project description:We used microarrays to compare the global programme of gene expression in HTLV-positive, ATL-derived and HTLV-positive in vitro-transformed cell lines with that of uninfected primary CD4 T cells.
