B-cell prolymphocytic leukemia
Ontology highlight
ABSTRACT:
ORGANISM(S): Homo sapiens
SUBMITTER: Dick de Ridder
PROVIDER: E-MTAB-1991 | biostudies-arrayexpress |
REPOSITORIES: biostudies-arrayexpress
Similar Datasets
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
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
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
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. Keywords: desease state analysis
2007-08-27 | GSE5788 | GEO
Project description:We investigated the pharmacological effects of the novel highly specific cyclin-dependent kinase 9 (CDK9) inhibitor LDC526 and its clinically used derivate atuveciclib employing primary T-PLL cells in an ex vivo drug sensitivity testing platform. All T-PLL samples were sensitive to CDK9 inhibition at submicromolar concentrations while conventional cytotoxic drugs were found to be largely ineffective. At the cellular level LDC526 inhibited the phosphorylation at serine 2 of the RNA polymerase II C-terminal domain resulting in decreased de novo RNA transcription. LDC526 induced apoptotic leukemic cell death through down-regulating MYC and MCL1 both at the mRNA and protein level. Microarray based transcriptomic profiling revealed that genes down-modulated in response to CDK9 inhibition were enriched for MYC and JAK-STAT targets. By contrast, CDK9 inhibition increased the expression of the tumor suppressor FBXW7 which may contribute to decreased MYC and MCL1 protein levels. The combination of atuvecliclib and the BCL2 inhibitor venetoclax exhibited synergistic anti-leukemic activity, providing the rationale for a novel targeted-agent based treatment of T-PLL.
2020-11-02 | GSE155747 | GEO
Project description:We investigated the pharmacological effects of the novel highly specific cyclin-dependent kinase 9 (CDK9) inhibitor LDC526 and its clinically used derivate atuveciclib employing primary T-PLL cells in an ex vivo drug sensitivity testing platform. All T-PLL samples were sensitive to CDK9 inhibition at submicromolar concentrations while conventional cytotoxic drugs were found to be largely ineffective. At the cellular level LDC526 inhibited the phosphorylation at serine 2 of the RNA polymerase II C-terminal domain resulting in decreased de novo RNA transcription. LDC526 induced apoptotic leukemic cell death through down-regulating MYC and MCL1 both at the mRNA and protein level. Microarray based transcriptomic profiling revealed that genes down-modulated in response to CDK9 inhibition were enriched for MYC and JAK-STAT targets. By contrast, CDK9 inhibition increased the expression of the tumor suppressor FBXW7 which may contribute to decreased MYC and MCL1 protein levels. The combination of atuvecliclib and the BCL2 inhibitor venetoclax exhibited synergistic anti-leukemic activity, providing the rationale for a novel targeted-agent based treatment of T-PLL.
2020-11-02 | GSE155746 | GEO
Project description:This SuperSeries is composed of the SubSeries listed below. Refer to individual Series
2013-05-07 | E-GEOD-46712 | biostudies-arrayexpress
Project description:We identified novel recurrent genetic lesions in T-PLL affecting genes involved in JAK/STAT signaling (PTPRC), epigenetic regulation (PRDM2), or DNA damage repair (SAMHD1, PARP10, HERC1, HERC2). Mutations of the tumor suppressor gene SAMHD1 causing amino-acid exchanges or protein truncations as well as copy number variations in SAMHD1 were seen in 20% of cases.
2018-07-23 | GSE100844 | GEO
Project description:We identified novel recurrent genetic lesions in T-PLL affecting genes involved in JAK/STAT signaling (PTPRC), epigenetic regulation (PRDM2), or DNA damage repair (SAMHD1, PARP10, HERC1, HERC2). Mutations of the tumor suppressor gene SAMHD1 causing amino-acid exchanges or protein truncations as well as copy number variations in SAMHD1 were seen in 20% of cases.
2018-02-22 | GSE100882 | GEO
Project description:Lgr5-EGFP-IRES-Cre-ERT2 mice were exposed to azoxymethane/dextrane sodium sulfate (AOM/DSS) which induces inflammation-driven colon tumors. Tumors were then flow-sorted into fractions of epithelial cells that expressed high or low levels of Lgr5. To exclude that transcriptional differences between Lgr5 high and low mouse colon tumor cells were imposed by distinct patterns of chromosomal aberrations in the two cell fractions, we also performed array comparative genomic hybridization (aCGH) from these tumors. All eight analyzed tumors were chromosomally stable, and thus, no difference between Lgr5 high and low cells could be detected. AOM/DSS-induced mouse colon tumors were flow-sorted into Lgr5 high and low cells before aCGH was performed. Biological replicates: 8. Two CGH array platforms.
2013-05-07 | E-GEOD-46711 | biostudies-arrayexpress