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The Human Epigenetic Drug Database (HEDD) is a comprehensive web-based database for epigenetic drugs, which focuses on the storage and integration of epigenetic drug datasets that were obtained from laboratory experiments that is essential for understanding the mechanism of action of these epigenetic drugs at a systematic level.

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Genome-wide DNA Methylation Analysis Reveals Novel Targets for Drug Development in Mantle Cell Lymphoma

Drug Name:5-aza-2'-deoxycytidine;Suberoylanilide hydroxamic acid
Drug Category:DNMTi;HDACi
Sample Type:human Mantle Cell Lymphoma (MCL) lines Mantle Cell Lymphoma (MCL) patients
Condition:mantle mell lymphoma,MCL
Experiment Type:Expression profiling by array;Methylation profiling by genome tiling array
Experiment Platform:GPL570 [HG-U133_Plus_2] Affymetrix Human Genome U133 Plus 2.0 Array GPL571 [HG-U133A_2] Affymetrix Human Genome U133A 2.0 Array GPL6604 HG17_HELP_Promoter
Description: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.
PubmedID:20427703
Citation:Leshchenko VV; Kuo PY;Shaknovich R; Yang DT; Gellen T;Petrich A; Yu Y; Remache Y;Weniger MA, Rafiq S;Suh KS; Goy A;Wilson W;Verma A; Braunschweig I; Muthusamy N;Kahl BS; Byrd JC;Wiestner A;Melnick A; Parekh S. Genomewide DNA methylation analysis reveals novel targets for drug development in mantle cell lymphoma. Blood 2010 Aug 19;116(7):1025-34
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The Human Epigenetic Drug Database (HEDD) is a comprehensive web-based database for epigenetic drugs, which focuses on integrating epigenetic drug studies based Omics data from high through experiments that is essential for understanding the mechanism of action of these epigenetic drugs at a systematic level.

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©2016 Group of Computational Epigenomics and Bioinformatics, College of Life Science, Jilin Normal University, China

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