Epigenetic inactivation of secreted Frizzled-related proteins in acute myeloid leukaemia

E. Jost, J. Schmid, S. Wilop, C. Schubert, H. Suzuki, J. G. Herman, R. Osieka, O. Galm

Research output: Contribution to journalArticle

Abstract

The Wnt signalling pathway has a key function in stem cell maintenance and differentiation of haematopoietic progenitors. Secreted Frizzled-related protein genes (SFRPs), functioning as Wnt signalling antagonists, have been found to be downregulated by promoter hypermethylation in many tumours. To analyse epigenetic dysregulation of SFRPs in acute myeloid leukaemia (AML), we examined the promoter methylation status of SFRP1, -2, -4 and -5 in AML cell lines by methylation-specific polymerase chain reaction (MSP). Aberrant CpG island methylation was found for all four SFRP genes. By real-time reverse transcription-PCR, corresponding transcriptional silencing for SFRP1 and -2 was demonstrated and treatment of cell lines with 5-aza-2′-deoxycytidine resulted in re-expression. The methylation status of the SFRP genes was analysed in 100 specimens obtained from AML patients at diagnosis. The frequencies of aberrant methylation among the patient samples were 29% for SFRP1, 19% for SFRP2, 0% for SFRP4 and 9% for SFRP5. For SFRP2, a correlation between promoter hypermethylation and transcriptional downregulation was found in primary AML samples. Among AML cases with a favourable karyotype, hypermethylation of SFRP genes was restricted to patients with core binding factor (CBF) leukaemia, and aberrant methylation of the SFRP2 promoter was an adverse risk factor for survival in CBF leukaemia.

Original languageEnglish (US)
Pages (from-to)745-753
Number of pages9
JournalBritish Journal of Haematology
Volume142
Issue number5
DOIs
StatePublished - Sep 2008

Fingerprint

Acute Myeloid Leukemia
Epigenomics
Methylation
Genes
Core Binding Factors
decitabine
Leukemia
Down-Regulation
Cell Line
Polymerase Chain Reaction
CpG Islands
Wnt Signaling Pathway
FRZB protein
Myeloid Cells
Karyotype
Reverse Transcription
Cell Differentiation
Stem Cells
Maintenance
Survival

Keywords

  • Acute myeloid leukaemia
  • Core binding factor leukaemia
  • Epigenetics
  • SFRP
  • Wnt pathway

ASJC Scopus subject areas

  • Hematology

Cite this

Jost, E., Schmid, J., Wilop, S., Schubert, C., Suzuki, H., Herman, J. G., ... Galm, O. (2008). Epigenetic inactivation of secreted Frizzled-related proteins in acute myeloid leukaemia. British Journal of Haematology, 142(5), 745-753. https://doi.org/10.1111/j.1365-2141.2008.07242.x

Epigenetic inactivation of secreted Frizzled-related proteins in acute myeloid leukaemia. / Jost, E.; Schmid, J.; Wilop, S.; Schubert, C.; Suzuki, H.; Herman, J. G.; Osieka, R.; Galm, O.

In: British Journal of Haematology, Vol. 142, No. 5, 09.2008, p. 745-753.

Research output: Contribution to journalArticle

Jost, E, Schmid, J, Wilop, S, Schubert, C, Suzuki, H, Herman, JG, Osieka, R & Galm, O 2008, 'Epigenetic inactivation of secreted Frizzled-related proteins in acute myeloid leukaemia', British Journal of Haematology, vol. 142, no. 5, pp. 745-753. https://doi.org/10.1111/j.1365-2141.2008.07242.x
Jost, E. ; Schmid, J. ; Wilop, S. ; Schubert, C. ; Suzuki, H. ; Herman, J. G. ; Osieka, R. ; Galm, O. / Epigenetic inactivation of secreted Frizzled-related proteins in acute myeloid leukaemia. In: British Journal of Haematology. 2008 ; Vol. 142, No. 5. pp. 745-753.
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