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Hypermethylation of the suppressor of cytokine signalling‐1 ( SOCS‐1 ) in myelodysplastic syndrome
Author(s) -
Brakensiek Kai,
Länger Florian,
Schlegelberger Brigitte,
Kreipe Hans,
Lehmann Ulrich
Publication year - 2005
Publication title -
british journal of haematology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.907
H-Index - 186
eISSN - 1365-2141
pISSN - 0007-1048
DOI - 10.1111/j.1365-2141.2005.05590.x
Subject(s) - cancer research , gene silencing , suppressor of cytokine signaling 1 , suppressor of cytokine signalling , methylation , dna methylation , socs2 , cytokine , socs3 , biology , suppressor , immunology , signal transduction , stat3 , gene expression , microbiology and biotechnology , gene , genetics
Summary Transcriptional silencing because of hypermethylation is now recognised to be a hallmark of human tumours. In contrast to acute myeloid leukaemia (AML), comparably little is known about aberrant methylation in myelodysplastic syndrome (MDS), a heterogeneous clonal stem cell disorder with a risk of transformation into secondary AML of up to 30%. Recent evidence demonstrates that suppressor of cytokine signalling SOCS‐1 , a negative regulator of cytokine pathways, may act as a tumour suppressor gene, and inactivation because of hypermethylation was shown in various malignancies. Employing a newly developed quantitative real‐time polymerase chain reaction‐based methylation assay we analysed, for the first time, SOCS‐1 methylation in MDS and found disease‐specific hypermethylation in 27 of 86 MDS patients (31%). Demethylation experiments provided direct evidence that aberrant methylation of SOCS‐1 induces transcriptional silencing in myeloid cells. In addition, by analysing the expression of signal transducers and activators of transcription (STAT)‐induced genes we provide for the first time evidence that the activity of the Janus kinase/STAT pathway is increased in primary patient samples showing SOCS‐1 hypermethylation.