Aberrant CpG island methylation in acute myeloid leukemia is accentuated at relapse

Heike Kroeger, Jaroslav Jelinek, Marcos R.H. Estecio, Rong He, Kimie Kondo, Woonbok Chung, Li Zhang, Lanlan Shen, Hagop M. Kantarjian, Carlos E. Bueso-Ramos, Jean Pierre J. Issa

Research output: Contribution to journalArticle

111 Citations (Scopus)

Abstract

DNA methylation of CpG islands around gene transcription start sites results in gene silencing and plays a role in leukemia pathophysiology. Its impact in leukemia progression is not fully understood. We performed genomewide screening for methylated CpG islands and identified 8 genes frequently methylated in leukemia cell lines and in patients with acute myeloid leukemia (AML): NOR1, CDH13, p15, NPM2, OLIG2, PGR, HIN1, and SLC26A4. We assessed the methylation status of these genes and of the repetitive element LINE-1 in 30 patients with AML, both at diagnosis and relapse. Abnormal methylation was found in 23% to 83% of patients at diagnosis and in 47% to 93% at relapse, with CDH13 being the most frequently methylated. We observed concordance in methylation of several genes, confirming the presence of a hypermethylator pathway in AML. DNA methylation levels increased at relapse in 25 of 30 (83%) patients with AML. These changes represent much larger epigenetic dysregulation, since methylation microarray analysis of 9008 autosomal genes in 4 patients showed hypermethylation ranging from 5.9% to 13.6% (median 8.3%) genes at diagnosis and 8.0% to 15.2% (median 10.6%) genes in relapse (P < .001). Our data suggest that DNA methylation is involved in AML progression and provide a rationale for the use of epigenetic agents in remission maintenance.

Original languageEnglish (US)
Pages (from-to)1366-1373
Number of pages8
JournalBlood
Volume112
Issue number4
DOIs
StatePublished - Aug 15 2008

Fingerprint

CpG Islands
Methylation
Acute Myeloid Leukemia
Genes
Recurrence
DNA Methylation
Leukemia
Epigenomics
Long Interspersed Nucleotide Elements
Transcription Initiation Site
Gene Silencing
Microarray Analysis
Microarrays
Maintenance
Screening
Cells
Cell Line

ASJC Scopus subject areas

  • Biochemistry
  • Immunology
  • Hematology
  • Cell Biology

Cite this

Kroeger, H., Jelinek, J., Estecio, M. R. H., He, R., Kondo, K., Chung, W., ... Issa, J. P. J. (2008). Aberrant CpG island methylation in acute myeloid leukemia is accentuated at relapse. Blood, 112(4), 1366-1373. https://doi.org/10.1182/blood-2007-11-126227

Aberrant CpG island methylation in acute myeloid leukemia is accentuated at relapse. / Kroeger, Heike; Jelinek, Jaroslav; Estecio, Marcos R.H.; He, Rong; Kondo, Kimie; Chung, Woonbok; Zhang, Li; Shen, Lanlan; Kantarjian, Hagop M.; Bueso-Ramos, Carlos E.; Issa, Jean Pierre J.

In: Blood, Vol. 112, No. 4, 15.08.2008, p. 1366-1373.

Research output: Contribution to journalArticle

Kroeger, H, Jelinek, J, Estecio, MRH, He, R, Kondo, K, Chung, W, Zhang, L, Shen, L, Kantarjian, HM, Bueso-Ramos, CE & Issa, JPJ 2008, 'Aberrant CpG island methylation in acute myeloid leukemia is accentuated at relapse', Blood, vol. 112, no. 4, pp. 1366-1373. https://doi.org/10.1182/blood-2007-11-126227
Kroeger, Heike ; Jelinek, Jaroslav ; Estecio, Marcos R.H. ; He, Rong ; Kondo, Kimie ; Chung, Woonbok ; Zhang, Li ; Shen, Lanlan ; Kantarjian, Hagop M. ; Bueso-Ramos, Carlos E. ; Issa, Jean Pierre J. / Aberrant CpG island methylation in acute myeloid leukemia is accentuated at relapse. In: Blood. 2008 ; Vol. 112, No. 4. pp. 1366-1373.
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