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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 in MDS/secondary AML and de novo AML

Drug Name:5-Azacytidine;Entinostat
Drug Category:DNMTi;HDACi
Sample Type:Bone marrow aspirates from 14 patients with MDS, MDS-associated AML (AML with trilineage dysplasia), chronic myelomonocytic leukemia, or relapsed AML
Condition: Acute Myelocytic Leukemia,AML
Experiment Type:Methylation profiling by genome tiling array
Experiment Platform:GPL6604 HG17_HELP_Promote
Description:Several of these diseases, such as myelodysplastic syndromes (MDSs), are responsive to DNA methyltransferase inhibitors. To determine the extent of promoter hypermethylation in such tumors, we compared the distribution of DNA methylation of 14 000 promoters in MDS and secondary acute myeloid leukemia (AML) patients enrolled in a phase 1 trial of 5-azacytidine and the histone deacetylase inhibitor entinostat against de novo AML patients and normal CD34(+) bone marrow cells. The MDS and secondary AML patients displayed more extensive aberrant DNA methylation involving thousands of genes than did the normal CD34(+) bone marrow cells or de novo AML blasts. Aberrant methylation in MDS and secondary AML tended to affect particular chromosomal regions, occurred more frequently in Alu-poor genes, and included prominent involvement of genes involved in the WNT and MAPK signaling pathways. DNA methylation was also measured at days 15 and 29 after the first treatment cycle. DNA methylation was reversed at day 15 in a uniform manner throughout the genome, and this effect persisted through day 29, even without continuous administration of the study drugs. Direct comparison of DNA methylation in bone marrow samples from patients with Myelodysplastic syndrome or secondary Acute Myeloid Leukemia (AML) at baseline and after in vivo treatment with 5-azacytidine + etinostat. A comparison to de novo normal karyotype AML was also performed. Two control groups were included: one consisting of 8 CD34+ bone marrow samples from healthy donors and a second one consisting of matched CD34+ and CD34- fractions from the bone marrows of 4 healthy donors.
PubmedID:19652201
Citation:Figueroa ME;Skrabanek L; Li Y; Jiemjit A; Fandy TE; Paietta E; Fernandez H;Tallman MS;Greally JM; Carraway H; Licht JD; Gore SD;Melnick A.MDS and secondary AML display unique patterns and abundance of aberrant DNA methylation. Blood2009 Oct 15;114(16):3448-58.
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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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