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Blood, 15 June 2004, Vol. 103, No. 12, pp. 4630-4635. Prepublished online as a Blood First Edition Paper on February 19, 2004; DOI 10.1182/blood-2003-06-2007. This Article Full Text (PDF) All Versions of this Article: 2003-06-2007v1 103/12/4630    most recent Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Rights and Permissions Citing Articles Citing Articles via HighWire Citing Articles via CrossRef Citing Articles via Google Scholar Google Scholar Articles by Chim, C.-S. Articles by Kwong, Y.-L. Search for Related Content PubMed PubMed Citation Articles by Chim, C.-S. Articles by Kwong, Y.-L. Related Collections Related Letter in Blood Online Social Bookmarking                   What's this? Submitted June 19, 2003 Accepted February 7, 2004 SOCS1 and SHP1 Hypermethylation in Multiple Myeloma: Implications for Epigenetic Activation of the Jak/STAT pathway Chor-Sang Chim, Tsz-Kin Fung, Wai-Chung Cheung, Raymond Liang, and Yok-Lam Kwong* Department of Medicine, University of Hong Kong, Hong Kong, China * Corresponding author; email: ylkwong{at}hkucc.hku.hk. SOCS1 and SHP1 negatively regulate the Jak/STAT signaling pathway. The role of promoter hypermethylation leading to epigenetic inactivation of SOCS1 and SHP1 in myeloma was investigated. The methylation-specific polymerase-chain-reaction, PCR (MSP) was used to define SOCS1 and SHP1 methylation in 34 diagnostic myeloma samples. For SOCS1, MSP primers 3' to the translation start site were unreliable and gave positive results in normal controls. However, primers in the 5' promoter region were specific, although no myeloma samples showed methylation. For SHP1, 27/34 (79.4%) myeloma samples showed SHP1 hypermethylation. The biologic significance of SHP1 methylation was investigated in the U266 human myeloma line. U266 contained completely methylated SHP1. Furthermore, there was constitutive STAT3 phosphorylation. Treatment with 5-azacytidine led to progressive de-methylation of SHP1 on days 2-5, with consequent increasing re-expression of SHP1 as shown by reverse-transcription PCR. Concomitant with increasing SHP1, a parallel down-regulation of phosphorylated STAT3 occurred, so that by day 5, phosphorylated STAT3 was barely detectable. The overall survivals of patients with and without SHP1 methylation were similar. SHP1 methylation leading to epigenetic activation of the Jak/STAT pathway might have a tentative role in the pathogenesis of myeloma, which should be further confirmed by functional studies in primary myeloma samples. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? Related Letter in Blood Online: Methylation of SHP1 gene and loss of SHP1 protein expression are frequent in systemic anaplastic large cell lymphoma Joseph D. Khoury, George Z. Rassidakis, L. Jeffrey Medeiros, Hesham M. Amin, and Raymond Lai Blood 2004 104: 1580-1581. [Full Text] [PDF] This article has been cited by other articles: M. K. Pandey, B. Sung, K. S. Ahn, and B. B. Aggarwal Butein Suppresses Constitutive and Inducible Signal Transducer and Activator of Transcription (STAT) 3 Activation and STAT3-Regulated Gene Products through the Induction of a Protein Tyrosine Phosphatase SHP-1 Mol. Pharmacol., March 1, 2009; 75(3): 525 - 533. [Abstract] [Full Text] [PDF] K. Nakase, J. Cheng, Q. Zhu, and W. A. Marasco Mechanisms of SHP-1 P2 promoter regulation in hematopoietic cells and its silencing in HTLV-1-transformed T cells J. Leukoc. Biol., January 1, 2009; 85(1): 165 - 174. [Abstract] [Full Text] [PDF] N. Fourouclas, J. Li, D. C. Gilby, P. J. Campbell, P. A. Beer, E. M. Boyd, A. C. 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Moller Biallelic mutation of SOCS-1 impairs JAK2 degradation and sustains phospho-JAK2 action in the MedB-1 mediastinal lymphoma line Blood, March 15, 2005; 105(6): 2535 - 2542. [Abstract] [Full Text] [PDF] J. D. Khoury, G. Z. Rassidakis, L. J. Medeiros, H. M. Amin, and R. Lai Methylation of SHP1 gene and loss of SHP1 protein expression are frequent in systemic anaplastic large cell lymphoma Blood, September 1, 2004; 104(5): 1580 - 1581. [Full Text] [PDF]

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