HOMEPRODUCTSCOMPANYCONTACTFAQResearchDictionaryPharmaSign Up FREE or Login

Methylation of the hMLH1 promoter and its association with microsatellite instability in acute myeloid leukemia.

Abstract
The hMLH1 and hMSH2 genes are involved in the DNA mismatch repair (MMR) pathway. Defects in either of these genes have been associated with genetic instability in a wide variety of malignancies. A molecular mechanism involved in aberrant MMR gene expression is the epigenetic silencing of transcription by promoter methylation. The importance of MMR promoter methylation in leukemia is presently unclear and we have therefore undertaken a detailed analysis of the promoter regions of hMLH1 and hMSH2 using the technique of bisulfite genomic sequencing. DNA from 55 patients with acute myeloid leukemia (AML) including 23 patients with therapy-related AML (t-AML) have been analyzed. Two patients with de novo AML demonstrated extensive methylation throughout the whole hMLH1 region sequenced, one of whom had previously shown widespread genetic instability, measured as microsatellite instability (MSI). However methylation of hMLH1 was not found in t-AML which has previously been associated with MSI. In addition, methylation was seen at a restricted region of the hMLH1 promoter in both AML patients and healthy controls. The significance of this methylated region of the hMLH1 promoter is uncertain, however, our results confirm that in some patients with AML extensive methylation of hMLH1, but not of hMSH2 may occur, and as is the case in solid tumors this can be associated with the presence of a defective DNA mismatch repair pathway resulting in MSI.
AuthorsC H Seedhouse, E P Das-Gupta, N H Russell
JournalLeukemia (Leukemia) Vol. 17 Issue 1 Pg. 83-8 (Jan 2003) ISSN: 0887-6924 [Print] England
PMID12529664 (Publication Type: Comparative Study, Journal Article, Research Support, Non-U.S. Gov't)
Chemical References
  • Adaptor Proteins, Signal Transducing
  • Carrier Proteins
  • DNA Primers
  • DNA, Neoplasm
  • DNA-Binding Proteins
  • MLH1 protein, human
  • Neoplasm Proteins
  • Nuclear Proteins
  • Proto-Oncogene Proteins
  • MSH2 protein, human
  • MutL Protein Homolog 1
  • MutS Homolog 2 Protein
Topics
  • Acute Disease
  • Adaptor Proteins, Signal Transducing
  • Adolescent
  • Aged
  • Base Pair Mismatch (genetics)
  • Carrier Proteins
  • Case-Control Studies
  • CpG Islands
  • DNA Methylation
  • DNA Primers (chemistry)
  • DNA Repair (genetics)
  • DNA, Neoplasm (genetics)
  • DNA-Binding Proteins
  • Female
  • Humans
  • Leukemia, Myeloid (genetics, therapy)
  • Male
  • Microsatellite Repeats
  • MutL Protein Homolog 1
  • MutS Homolog 2 Protein
  • Neoplasm Proteins (genetics, metabolism)
  • Nuclear Proteins
  • Polymerase Chain Reaction
  • Promoter Regions, Genetic
  • Proto-Oncogene Proteins (genetics, metabolism)

Join CureHunter, for free Research Interface BASIC access!

Take advantage of free CureHunter research engine access to explore the best drug and treatment options for any disease. Find out why thousands of doctors, pharma researchers and patient activists around the world use CureHunter every day.
Realize the full power of the drug-disease research graph!


Choose Username:
Email:
Password:
Verify Password:
Enter Code Shown: