Aberrant DNA methylation is a dominant mechanism in MDS progression to AML (Blood, 2009, 113:1315-1325)

報告日期: 2009/04/17
報告時間: 15:10/16:00
報告學生: 郭懿瑩
講評老師: 劉校生
附件下載:

http://basicmed.med.ncku.edu.tw/admin/up_img/980417-1.pdf

Aberrant DNA methylation is a dominant mechanism in MDS progression to AML

Ying Jiang, Andrew Dunbar, Lukasz P. Gondek, Sanjay Mohan, Manjot Rataul, Christine O’Keefe, Mikkael Sekeres, Yogen Saunthararajah, and Jaroslaw P. Maciejewski

 

Blood, 113:1315-1325, 2009

 

Commentator: Liu, Hsiao-Sheng, Ph.D. (劉校生教授)

Speaker: Kuo, Yih-Ying (郭懿瑩)

Time/Date: 15:10-16:00, April 17, 2009

Room: 602

 

Abstract

Epigenetic modification of DNA is an important biological function regulating gene expression in normal and tumor cells. Myelodysplastic syndromes (MDS) are a heterogenous group of hematopoietic stem cell disorders that are multifactorial in their etiology. Unique genetic alterations in combinations or in isolation account for a small fraction of MDS suggesting the epigenetic hypermethylation as a possible leading cause for MDS and its transformation to acute myelocytic leukemia (AML). In these studies, authors use gene array technologies to assess the extent of aberrant DNA methylation and chromosome aberrations in bone marrow samples from 184 patients with MDS or AML. They found that aberrant methylations were significantly greater in patients with refractory anemia with excess of blast (RAEB)/AML compared with patient with low-risk MDS. In contrast, chromosome aberrations were seen in 79% of low-risk MDS samples and 90% of RAEB/AML samples. Therefore, the authors thought aberrant DNA hypermethylation was detected much more frequently than chromosome aberrations. Analysis of the most frequently aberrantly methylated genes identified FZD9 as a candidate TSG on chromosome 7, these results to indicate that aberrant methylation can cooperate with chromosome deletions to silence TSG, which may account in the part for the poor prognosis associated with deletion of certain chromosome in myeloid malignancies.

 

References:

1.     Michael Grovdal et al., Negative Effect of DNA Hypermethylation on the Outcome of Intensive Chemotherapy in Older Patients with High-Risk Myelodysplastic Syndromes and AcuteMyeloid Leukemia following Myelodysplastic Syndrome. Clin Cancer Res, 13:7101-7112, 2007.

2.     LP Gondek et al., Single nucleotide polymorphism arrays complement metaphase cytogenetics in detection of new chromosomal lesions in MDS. Leukemia, 21: 2058–2061, 2007.