Large-scale analysis of DNA methylation in chronic lymphocytic leukemia

Farahnaz B. Rahmatpanah, Stephanie Carstens, Sam I. Hooshmand, Elise C. Welsh, Ozy Sjahputera, Kristen H. Taylor, Lynda B. Bennett, Huidong Shi, J. Wade Davis, Gerald L. Arthur, Tait D. Shanafelt, Neil E. Kay, James E. Wooldridge, Charles W. Caldwell

Research output: Contribution to journalArticlepeer-review

42 Scopus citations

Abstract

Aims: B-cell chronic lymphocytic leukemia (CLL) is a heterogeneous malignancy that clinically ranges from indolent to rapidly progressive. CLL, like other cancers, can be affected by epigenetic alterations. Materials & methods: A microarray discovery-based study was initiated to determine DNA methylation in CLL cases with a range of CD38 expression (1-92%). Results: Many loci were either methylated or unmethylated across all CD38 levels, but differential methylation was also observed for some genes. Genomic sequencing of DLEU7 confirmed extensive cytosine methylation preferentially in patient samples with low CD38 expression, whereas NRP2, SFRP2 and ADAM12 were more commonly methylated in those with high CD38 expression. Conclusion: This study demonstrates that CLL is affected by CpG island methylation in some genes that segregate with CD38 expression levels, while most others show similar methylation patterns across all levels. The CpG island methylation in certain functional gene groups and pathway-associated genes that are known to be deregulated in CLL provides additional insights into the CLL methylome and epigenetic contribution to cellular dysfunction. It will now be useful to investigate the effectiveness of epigenetic therapeutic reversal of these alterations to develop effective treatments for the disease.

Original languageEnglish (US)
Pages (from-to)39-61
Number of pages23
JournalEpigenomics
Volume1
Issue number1
DOIs
StatePublished - Oct 2009
Externally publishedYes

Keywords

  • CD38 expression
  • CLL
  • DNA methylation
  • Epigenetics
  • Leukemia

ASJC Scopus subject areas

  • Genetics
  • Cancer Research

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