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DNA demethylating agents and EZH2 inhibitors for Adult T cell leukemia [Illumina]

ABSTRACT: 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.

ORGANISM(S): Homo sapiens

PROVIDER: GSE189602 | GEO | 2023/05/03

REPOSITORIES: GEO

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DNA demethylating agents and EZH2 inhibitors for Adult T cell leukemia [Affymetrix]

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.

2023-05-03 | GSE189603 | GEO

Highly selective HSP90 inhibitor, pimitespib, demonstrates its potent growth suppressive activity to adult T-cell leukemia in preclinical models (OATL4).

Project description:Adult T-cell leukaemia-lymphoma (ATL) is a highly chemoresistant malignancy of peripheral T lymphocytes caused by human T-lymphotropic virus type I (HTLV-1). ATL cells constitutively activate anti-apoptotic signals through nuclear factor kappaB (NF-κB)-mediated gene expression. The molecular chaperon heat shock protein 90 (HSP90) plays a crucial role on NF-κB-mediated anti-apoptotic activity in ATL cells and HSP90 inhibitors, such as 17-DMAG and NVP-AUY922, have demonstrated their anti-ATL activities. A novel class of orally active inhibitors of cytosolic HSP90α and β, pimitespib, demonstrated its highly selective anti-ATL cell effects both ex-vivo and in vivo preclinical models. Ten ATL-related cell lines achieved their IC50 below 0.5µM dose of TAS-116 while CD4 lymphocytes derived from healthy donors were less harmed than ATL cells. TAS-116 efficiently induces Tax-degradation and IκB-α accumulation to Tax-positive cell-lines. DNA microarray profiling followed by a variety of pathway analysis revealed that TAS-116 down-regulated NF-κB activating pathways in Tax-positive cells and cell cycle promoting pathways in Tax-negative cells and induces anti-ATL effect. Oral administration of TAS-116 to ATL-cell xenograft model mice also demonstrated the growth inhibitory effects against tumor cells. Consequently, TAS-116, one of the most evolved HSP90 inhibitor, may become a promising option against ATL therapy.

2022-02-18 | GSE168556 | GEO

Highly selective HSP90 inhibitor, pimitespib, demonstrates its potent growth suppressive activity to adult T-cell leukemia in preclinical models (LYM1, KK1).

2022-02-18 | GSE168555 | GEO

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2022-02-18 | GSE168554 | GEO

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2022-02-18 | GSE168558 | GEO

Highly selective HSP90 inhibitor, pimitespib, demonstrates its potent growth suppressive activity to adult T-cell leukemia in preclinical models (Pt1-3).

2022-02-18 | GSE168557 | GEO

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miRNA expression profiling in Adult T-cell Leukemia (ATL) cells and in Normal CD4+ T-cells

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.

2012-02-23 | E-GEOD-31629 | biostudies-arrayexpress

Genome-wide analysis of gene expression profiles in individuals infected with the Human T-Lymphotropic virus Type 1 (HTLV-1)

Project description:This SuperSeries is composed of the following subset Series: GSE29312: Genome-wide analysis of gene expression profiles in individuals infected with the Human T-Lymphotropic virus Type 1 (HTLV-1) - train set GSE29332: Genome-wide analysis of gene expression profiles in individuals infected with the Human T-Lymphotropic virus Type 1 (HTLV-1) - test set Refer to individual Series

2012-01-01 | E-GEOD-29333 | biostudies-arrayexpress

Whole genome gene expression profiling in Adult T-cell Leukemia (ATL) cells and in Normal CD4+ T-cells

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.

2012-02-23 | E-GEOD-33615 | biostudies-arrayexpress

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