Tumor biopsies from 71 untreated patients with mantle cell lymphoma
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ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE10793 | GEO | 2008/04/01
SECONDARY ACCESSION(S): PRJNA107489
REPOSITORIES: GEO
Similar Datasets
Project description:The proliferation gene expression signature is a quantitative integrator of oncogenic events that predicts survival in mantle cell lymphoma Keywords: lymphochip; MCL; untreated Tumor biopsies from 71 untreated patients with mantle cell lymphoma
2010-05-23 | E-GEOD-10793 | biostudies-arrayexpress
Project description:The genome of mantle cell lymphoma (MCL) is, in addition to the translocation t(11;14), characterized by a high number of secondary chromosomal gains and losses that likely account for the varying survival times of MCL patients. We investigated 77 primary MCL tumors with available clinical information using high resolution RNA expression and genomic profiling and applied our recently developed gene expression and dosage integrator (GEDI) algorithm to identify novel genes and pathways that may be of relevance for the pathobiology of MCL. We show that copy number neutral loss of heterozygosity (CNN-LOH) is common in MCL and targets regions that are frequently affected by deletions. The molecular consequences of genomic copy number changes appear complex, even in genomic loci with identified tumor suppressors, such as the region 9p21 containing the CDKN2A locus. Moreover, the deregulation of novel genes such as CUL4A, ING1 and MCPH1 may affect the two crucial pathogenetic mechanisms in MCL, the disturbance of the proliferation and DNA damage response pathways. Deregulation of the Hippo pathway may have a pathogenetic role in MCL, since decreased expression of its members MOBKL2A, MOBKL2B and LATS2 was associated with inferior outcome also in an independent validation series of 32 MCL. Sixty-four primary MCL specimens from previously untreated patients were investigated with Affymetrix HG U133 plus 2.0 gene expression arrays.
2011-03-31 | E-GEOD-21452 | biostudies-arrayexpress
Project description:The genome of mantle cell lymphoma (MCL) is, in addition to the translocation t(11;14), characterized by a high number of secondary chromosomal gains and losses that likely account for the varying survival times of MCL patients. We investigated 77 primary MCL tumors with available clinical information using high resolution RNA expression and genomic profiling and applied our recently developed gene expression and dosage integrator (GEDI) algorithm to identify novel genes and pathways that may be of relevance for the pathobiology of MCL. We show that copy number neutral loss of heterozygosity (CNN-LOH) is common in MCL and targets regions that are frequently affected by deletions. The molecular consequences of genomic copy number changes appear complex, even in genomic loci with identified tumor suppressors, such as the region 9p21 containing the CDKN2A locus. Moreover, the deregulation of novel genes such as CUL4A, ING1 and MCPH1 may affect the two crucial pathogenetic mechanisms in MCL, the disturbance of the proliferation and DNA damage response pathways. Deregulation of the Hippo pathway may have a pathogenetic role in MCL, since decreased expression of its members MOBKL2A, MOBKL2B and LATS2 was associated with inferior outcome also in an independent validation series of 32 MCL.
2011-04-01 | GSE21452 | GEO
Project description:In this study we compared the expression of 30215 genes in mantle cell lymphoma-initiating cells (MCL-ICs) with mantle cell lymphoma-non-initiating cells (MCL-non-ICs) and B-cells from healthy donor
2014-08-02 | GSE60023 | GEO
Project description:In this study we compared the expression of 30215 genes in mantle cell lymphoma-initiating cells (MCL-ICs) with mantle cell lymphoma-non-initiating cells (MCL-non-ICs) and B-cells from healthy donor Three samples each of MCL-ICs and MCL-non-ICs were isolated from aphresis of 3 mantle cell lymphoma primary patient samples and 2 samples of CD19+ Bcells isolated from buffy coats of healthy donor Microarray include both coding and non-coding transcripts but only mRNA coding transcript were included in this study.
2014-08-02 | E-GEOD-60023 | biostudies-arrayexpress
Project description:The genes regulated by SOX11 in MCL was investigated in MCL cell line Granta 519 by siRNA knock down system. Cells were transfected using the LONZA electroporation system. Results represent cells harvested after 20 hours. Details of the experiment is published in PMID 21124928. Gene expression profiles (Human Gene 1.0 ST) of mantle cell lymphoma (MCL) cell line Granta 519 treated with SOX11 siRNA. Data analyses were performed using the Affymetrix Expression Console (v. 1.1)
2010-11-29 | E-GEOD-25621 | biostudies-arrayexpress
Project description:Mantle Cell lymphoma (MCL) were treated with the BTK inhibitor 1mM CC-292 for 48h We used microarrays to uncover the mechanisms underlying CC-292 activity in Mantle Cell lymphoma (MCL)
2017-09-01 | GSE94328 | GEO
Project description:Loss of function mutations in the histone methyltransferase KMT2D are common in lymphomas but difficult to target. We reported targeting KDM5 restores epigenetic balance in germinal centre (GC) lymphomas. Here, we show the KDM5 family are over-expressed in mantle cell lymphoma (MCL). GS716054, a pro-drug, increases H3K4 trimethylation (H3K4me3) and kills MCL cells including TP53 mutated cells via suppression of the MYC pathway. It can overcome ibrutinib resistance and synergises with ibrutinib. These data suggest a possible role for KDM5-inhibitors in advanced MCL.
2024-09-24 | GSE243395 | GEO
Project description:Ibrutinib, a bruton's tyrosine kinase inhibitor, was shown to have high response rates in mantle cell lymphoma (MCL), an aggressive B-cell lymphoma. However, emergence of ibrutinib resistance (IR) and subsequent fatal progression is of significant clinical concern. By implementing genomics, chemical proteomics and drug screening, we report that enhancer remodeling-mediated transcriptional activation and adaptive signaling changes drive the malignant phenotype of IR. Accordingly, IR MCL cells are vulnerable to inhibition of the transcriptional machinery and especially to inhibition of cyclin-dependent kinase 9 (CDK9). Thus, targeting transcriptional activation offers a novel strategy to prevent the emergence of IR and overcome IR via impeding IR-associated cellular signaling reprogramming in MCL. In addition, our ex-vivo microfluidic image-based functional drug screen can function not only as new technology platforms for predicting clinical therapeutic response but also, in conjunction with genomic profiling in primary MCL samples, identify the molecular vulnerabilities for drug resistance evolution, providing insight into the underlying IR mechanisms for MCL and other B-cell malignancies
2021-04-26 | GSE141335 | GEO
Project description:Mantle Cell Lymphoma (MCL) is a mostly incurable malignancy arising from naïve B cells (NBC) in the mantle zone of lymph node follicles. We analyzed genome-wide methylation in MCL patients using the HELP (Hpa II tiny fragment Enrichment by Ligation mediated PCR) assay and found significant aberrancy in promoter methylation patterns as compared to normal NBCs. Using biological and stringent statistical criteria, we further identified four hypermethylated genes CDKN2B, MLF-1, PCDH8, HOXD8 and four hypomethylated genes CD37, HDAC1, NOTCH1 and CDK5 where aberrant methylation was associated with inverse changes in mRNA levels. MassArray Epityper analysis confirmed the presence of differential methylation at the promoter region of these genes. Immunohistochemical analysis of an independent cohort of 14 MCL patient samples, confirmed CD37 surface expression in 93% of patients, validating its selection as a target for MCL therapy. Treatment of MCL cell lines with a novel small modular immunopharmaceutical(CD37-SMIP) resulted in significant loss of viability in cell lines with intense surface CD37 expression. Treatment of MCL cell lines with the DNA methyltransferase inhibitor decitabine resulted in reversal of aberrant hypermethylation and synergized with the HDAC inhibitor SAHA in induction of the four hypermethylated genes CDKN2B, MLF-1, PCDH8 and HOXD8. The combination of Decitabine and SAHA also resulted in potent and synergistic anti-MCL cytotoxicity as compared to either drug alone. In conclusion, our analysis shows prominent and aberrant methylation of the MCL genome and identifies novel differentially methylated and expressed genes in MCL cell lines and patient samples. Furthermore, our data suggest that differentially methylated genes can be targeted for therapeutic benefit in MCL. Gene expression profiling by array comprised of 8 mantle cell lymphoma (MCL) cell lines and 8 leukemic blast from blood from patients newly diagnosed with MCL. Unbiased genome-wide analysis of DNA methylation in leukemic blast from peripheral blood or pheresis products from 22 patients newly diagnosed with mantle cell lymphoma (MCL) prior to any treatment. 10 IgD+ Na ve B cells from specimens from healthy donors undergoing routine tonsillectomy were used as appropriate controls. Methylation patterns of 13 MCL cell lines were also compared.
2010-07-30 | E-GEOD-19243 | biostudies-arrayexpress