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Suppressor of cytokine signalling‐1 gene silencing in acute myeloid leukaemia and human haematopoietic cell lines
Author(s) -
Watanabe Dai,
Ezoe Sachiko,
Fujimoto Minoru,
Kimura Akihiro,
Saito Yoshiyuki,
Nagai Hisaki,
Tachibana Isao,
Matsumura Itaru,
Tanaka Toshio,
Kanegane Hirokazu,
Miyawaki Toshio,
Emi Mitsuru,
Kanakura Yuzuru,
Kawase Ichiro,
Naka Tetsuji,
Kishimoto Tadamitsu
Publication year - 2004
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.1365-2141.2004.05107.x
Subject(s) - haematopoiesis , suppressor of cytokine signaling 1 , cancer research , biology , suppressor of cytokine signalling , gene silencing , jurkat cells , dna methylation , socs3 , cytokine , myeloid , tumor suppressor gene , transfection , socs5 , cell culture , suppressor , tyrosine kinase , immunology , gene , carcinogenesis , gene expression , microbiology and biotechnology , signal transduction , t cell , genetics , stem cell , immune system
Summary The aim of this study was to investigate whether the suppressor of cytokine signalling (SOCS)‐1 can act as a tumour suppressor when functioning as a negative regulator of the Janus family tyrosine kinases (JAKs), which have been reported to play important roles in leukaemogenesis. For this purpose, we carried out molecular analysis of the SOCS‐1 gene in human acute myeloid leukaemia (AML) and human haematopoietic cell lines. Sequencing alterations in the coding region were found in two of 90 primary AML samples and one of 17 cell lines. Hypermethylation of the SOCS‐1 gene was also observed in 72% of primary cases and 52% of cell lines and aberrant methylation strongly correlated with reduced expression. Transfection of SOCS‐1 into Jurkat cells harbouring the mutation and methylation suppressed cell growth at a low serum concentration. These findings indicate that SOCS‐1 is frequently silenced in haematopoietic malignancies, mainly as a result of hypermethylation, and suggest that SOCS‐1 may be able to function as a tumour suppressor.