J Korean Med Sci.  2011 Feb;26(2):207-213. 10.3346/jkms.2011.26.2.207.

DNA Methylation Changes Following 5-azacitidine Treatment in Patients with Myelodysplastic Syndrome

• Tran HT
• Kim HN
• Lee IK
• Kim YK
• Ahn JS
• Yang DH
• Lee JJ
• Kim HJ

• KMID: 1782108
• DOI: http://doi.org/10.3346/jkms.2011.26.2.207

Abstract

DNA methyltransferase inhibitor, 5-azacitidine (AC) is effective in myelodysplastic syndromes (MDS) and can induce re-expression in cancer. We analyzed the methylation of 25 tumor suppressor genes in AC-treated MDS. Hypermethylation of CDKN2B, FHIT, ESR1, and IGSF4 gene was detected in 9/44 patients. In concordance with the clinical response, a lack of or decreased methylation in 4 patients with hematologic improvements and persistent methylation in 4 others with no response was observed. The mRNA expression of CDKN2B, IGSF4, and ESR1 was significantly reduced in MDS. Our results suggest that methylation changes contribute to disease pathogenesis and may serve as marker to monitor the efficacy of treatments.

Keyword

Demethylation; DNA Methylation; Myelodysplastic Syndromes; DNA Methyltransferase Inhibitors; Azacitidine; MS-MLPA

MeSH Terms

Adolescent
Adult
Aged
Aged, 80 and over
Azacitidine/*pharmacology/*therapeutic use
DNA Methylation/*drug effects
DNA Modification Methylases/antagonists & inhibitors/metabolism
Enzyme Inhibitors/*pharmacology/*therapeutic use
Female
Genes, Tumor Suppressor
Humans
Male
Middle Aged
Myelodysplastic Syndromes/*drug therapy/*genetics
Young Adult

Figure

• 

  Fig. 1 Quantitative analysis of mRNA expression of CDKN2B, FHIT, IGSF4, and ESR1 in 30 MDS patients and 16 normal controls were analyzed at diagnosis. MDS group was significantly lower level in CDKN2B, IGSF4, and ESR1 (P < 0.05). The horizontal bars indicate the median value for each sample group.

• 

  Fig. 2 Demethylation due to AC treatment in the methylated samples was associated with mRNA re-expression in the MDS group after 3-5 treatment cycles. Data shown are representative of three independent experiments. P means patient number.

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