Suppressor of cytokine signalling-1 gene silencing in acute myeloid leukaemia and human haematopoietic cell lines.
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.
Laboratory of Immune Regulation, Osaka University Graduate School of Frontier Biosciences, 1-3 Yamada-oka, Suita City, Osaka 565-0871, Japan. dai@imed3.med.osaka-u.ac.jp
Dai
D
Watanabe
Sachiko
S
Ezoe
Minoru
M
Fujimoto
Akihiro
A
Kimura
Yoshiyuki
Y
Saito
Hisaki
H
Nagai
Isao
I
Tachibana
Itaru
I
Matsumura
Toshio
T
Tanaka
Hirokazu
H
Kanegane
Toshio
T
Miyawaki
Mitsuru
M
Emi
Yuzuru
Y
Kanakura
Ichiro
I
Kawase
Tetsuji
T
Naka
Tadamitsu
T
Kishimoto
D000208:Acute Disease; D002352:Carrier Proteins / Q000235:genetics*; D002460:Cell Line; D045744:Cell Line, Tumor; D020868:Gene Silencing; D016147:Genes, Tumor Suppressor; D019337:Hematologic Neoplasms / Q000378:metabolism; D006410:Hematopoiesis / Q000502:physiology; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins; D019169:Jurkat Cells; D007951:Leukemia, Myeloid / Q000378:metabolism*; D008745:Methylation; D012097:Repressor Proteins / Q000235:genetics*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D017422:Sequence Analysis, DNA; D000071222:Suppressor of Cytokine Signaling 1 Protein; D050826:Suppressor of Cytokine Signaling Proteins
D002352:Carrier Proteins; D047908:Intracellular Signaling Peptides and Proteins; D012097:Repressor Proteins; C108944:SOCS1 protein, human; D000071222:Suppressor of Cytokine Signaling 1 Protein; D050826:Suppressor of Cytokine Signaling Proteins