Project description:MCL cell lines were treated with DMSO or 5uM AFN700 for 20hrs This experiment is designed to see if NFKB-target genes are downregulated by inhibition of IKKB in MCL cell lines that are insensitive to ibrutinib (BTK inhibitor) or sotrastaurin (PKC inhibitor) MCL cells were seeded in 6well dishes and treated for 20hrs with DMSO or 5uM AFN700
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)
Project description:The RNA-seq data presented in this study include libraries from Mantle Cell Lymphoma (MCL) tumor cells of 4 patients, Peripheral Blood B Cells from 3 healthy volunteers and JEKO-1 MCL cell lines
Project description:MCL cell lines were treated with DMSO or 5uM AFN700 for 20hrs This experiment is designed to see if NFKB-target genes are downregulated by inhibition of IKKB in MCL cell lines that are insensitive to ibrutinib (BTK inhibitor) or sotrastaurin (PKC inhibitor)
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
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.
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.
