Suppressor of cytokine signalling-1 gene silencing in acute myeloid leukaemia and human haematopoietic cell lines

Dai Watanabe, Sachiko Ezoe, Minoru Fujimoto, Akihiro Kimura, Yoshiyuki Saito, Hisaki Nagai, Isao Tachibana, Itaru Matsumura, Toshio Tanaka, Hirokazu Kanegane, Toshio Miyawaki, Mitsuru Emi, Yuzuru Kanakura, Ichiro Kawase, Tetsuji Naka, Tadamitsu Kishimoto

Research output: Contribution to journalArticle

59 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)726-735
Number of pages10
JournalBritish Journal of Haematology
Volume126
Issue number5
DOIs
Publication statusPublished - 2004 Sep

Fingerprint

Gene Silencing
Acute Myeloid Leukemia
Cytokines
Cell Line
Methylation
Jurkat Cells
Hematologic Neoplasms
Protein-Tyrosine Kinases
Genes
Transfection
Neoplasms
Mutation
Growth
Serum

Keywords

  • Acute myeloid leukaemia
  • Janus family tyrosine kinases
  • Methylation
  • Suppressor of cytokine signalling-1
  • Tumour suppressor

ASJC Scopus subject areas

  • Hematology

Cite this

Suppressor of cytokine signalling-1 gene silencing in acute myeloid leukaemia and human haematopoietic cell lines. / 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.

In: British Journal of Haematology, Vol. 126, No. 5, 09.2004, p. 726-735.

Research output: Contribution to journalArticle

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 2004, 'Suppressor of cytokine signalling-1 gene silencing in acute myeloid leukaemia and human haematopoietic cell lines', British Journal of Haematology, vol. 126, no. 5, pp. 726-735. https://doi.org/10.1111/j.1365-2141.2004.05107.x
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. / Suppressor of cytokine signalling-1 gene silencing in acute myeloid leukaemia and human haematopoietic cell lines. In: British Journal of Haematology. 2004 ; Vol. 126, No. 5. pp. 726-735.
@article{179bce61caf848f58ca36b16023660d6,
title = "Suppressor of cytokine signalling-1 gene silencing in acute myeloid leukaemia and human haematopoietic cell lines",
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.",
keywords = "Acute myeloid leukaemia, Janus family tyrosine kinases, Methylation, Suppressor of cytokine signalling-1, Tumour suppressor",
author = "Dai Watanabe and Sachiko Ezoe and Minoru Fujimoto and Akihiro Kimura and Yoshiyuki Saito and Hisaki Nagai and Isao Tachibana and Itaru Matsumura and Toshio Tanaka and Hirokazu Kanegane and Toshio Miyawaki and Mitsuru Emi and Yuzuru Kanakura and Ichiro Kawase and Tetsuji Naka and Tadamitsu Kishimoto",
year = "2004",
month = "9",
doi = "10.1111/j.1365-2141.2004.05107.x",
language = "English",
volume = "126",
pages = "726--735",
journal = "British Journal of Haematology",
issn = "0007-1048",
publisher = "Wiley-Blackwell",
number = "5",

}

TY - JOUR

T1 - Suppressor of cytokine signalling-1 gene silencing in acute myeloid leukaemia and human haematopoietic cell lines

AU - Watanabe, Dai

AU - Ezoe, Sachiko

AU - Fujimoto, Minoru

AU - Kimura, Akihiro

AU - Saito, Yoshiyuki

AU - Nagai, Hisaki

AU - Tachibana, Isao

AU - Matsumura, Itaru

AU - Tanaka, Toshio

AU - Kanegane, Hirokazu

AU - Miyawaki, Toshio

AU - Emi, Mitsuru

AU - Kanakura, Yuzuru

AU - Kawase, Ichiro

AU - Naka, Tetsuji

AU - Kishimoto, Tadamitsu

PY - 2004/9

Y1 - 2004/9

N2 - 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.

AB - 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.

KW - Acute myeloid leukaemia

KW - Janus family tyrosine kinases

KW - Methylation

KW - Suppressor of cytokine signalling-1

KW - Tumour suppressor

UR - http://www.scopus.com/inward/record.url?scp=4544358147&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=4544358147&partnerID=8YFLogxK

U2 - 10.1111/j.1365-2141.2004.05107.x

DO - 10.1111/j.1365-2141.2004.05107.x

M3 - Article

C2 - 15327527

AN - SCOPUS:4544358147

VL - 126

SP - 726

EP - 735

JO - British Journal of Haematology

JF - British Journal of Haematology

SN - 0007-1048

IS - 5

ER -