RRC ID 1933
Author Watanabe D, Ezoe S, Fujimoto M, Kimura A, Saito Y, Nagai H, Tachibana I, Matsumura I, Tanaka T, Kanegane H, Miyawaki T, Emi M, Kanakura Y, Kawase I, Naka T, Kishimoto T.
Title Suppressor of cytokine signalling-1 gene silencing in acute myeloid leukaemia and human haematopoietic cell lines.
Journal Br. J. Haematol.
Abstract 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.
Volume 126(5)
Pages 726-35
Published 2004-9
DOI 10.1111/j.1365-2141.2004.05107.x
PMID 15327527
IF 5.206
Times Cited 61
Human and Animal Cells Jurkat(RCB0806)