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Conference Paper: Receptor-type tyrosine-protein phosphatase kappa promoter hypermethylation correlates with unfavorable prognosis in nasal NK/T-cell lymphoma patients treated with SMILE regimen

TitleReceptor-type tyrosine-protein phosphatase kappa promoter hypermethylation correlates with unfavorable prognosis in nasal NK/T-cell lymphoma patients treated with SMILE regimen
Authors
Issue Date2014
Citation
The 60th Autumn Annual Meeting of the Japanese Society of Pathology, Okinawa, Japan, 20-21 November 2014. How to Cite?
AbstractOne of the main characteristics of nasal NK/T-cell lymphoma (NKTCL) is the constitutive activation of signal transducer and activator of transcription 3 (STAT3) and frequent deletions on chromosome 6q. Tyrosine phosphorylation at Tyr705 is required for STAT3 to bind to specific DNA target sites. Here we first investigated whether receptor-type tyrosine-protein phosphatase kappa (PTPRK), the only protein tyrosine phosphatase at 6q that contains a STAT3-specifying motif, negatively regulates STAT3 activation in NKTCL. We found a strong in vivo correlation between low PTPRK expression and high nuclear phospho-STAT3Tyr705 levels in NKTCL primary tumors and showed that PTPRK binds to STAT3 and directly dephosphorylates phospho-STAT3 at Tyr705 and regulates the levels of phospho-STAT3Tyr705 in NKTCL. Further studies showed that monoallelic deletion and promoter hypermethylation causes underexpression of PTPRK mRNA in NKTCL, and methylation of PTPRK promoter significantly correlates with higher IPI (p<0.001) and with inferior overall survival (p=0.049) in NKTCL patients treated with the steroid-dexamethasone, methotrexate, ifosfamide, L-asparaginase, and etoposide (SMILE) regimen. Altogether, our findings show that PTPRK underexpression leads to STAT3 activation and contributes to NKTCL pathogenesis and that methylation of the PTPRK promoter correlates with a severe clinical course and worse prognosis in NKTCL patients treated with the SMILE protocol.
DescriptionPoster Presentation: no. IP-1
ポスター演題プログラム: IP-1
Persistent Identifierhttp://hdl.handle.net/10722/211532

 

DC FieldValueLanguage
dc.contributor.authorAu Yeung, RKH-
dc.contributor.authorChen, WYW-
dc.contributor.authorGuo, T-
dc.contributor.authorWong, KY-
dc.contributor.authorShimizu, N-
dc.contributor.authorTsuchiyama, J-
dc.contributor.authorLoong, F-
dc.contributor.authorKwong, YL-
dc.contributor.authorSrivastava, G-
dc.date.accessioned2015-07-16T07:10:06Z-
dc.date.available2015-07-16T07:10:06Z-
dc.date.issued2014-
dc.identifier.citationThe 60th Autumn Annual Meeting of the Japanese Society of Pathology, Okinawa, Japan, 20-21 November 2014.-
dc.identifier.urihttp://hdl.handle.net/10722/211532-
dc.descriptionPoster Presentation: no. IP-1-
dc.descriptionポスター演題プログラム: IP-1-
dc.description.abstractOne of the main characteristics of nasal NK/T-cell lymphoma (NKTCL) is the constitutive activation of signal transducer and activator of transcription 3 (STAT3) and frequent deletions on chromosome 6q. Tyrosine phosphorylation at Tyr705 is required for STAT3 to bind to specific DNA target sites. Here we first investigated whether receptor-type tyrosine-protein phosphatase kappa (PTPRK), the only protein tyrosine phosphatase at 6q that contains a STAT3-specifying motif, negatively regulates STAT3 activation in NKTCL. We found a strong in vivo correlation between low PTPRK expression and high nuclear phospho-STAT3Tyr705 levels in NKTCL primary tumors and showed that PTPRK binds to STAT3 and directly dephosphorylates phospho-STAT3 at Tyr705 and regulates the levels of phospho-STAT3Tyr705 in NKTCL. Further studies showed that monoallelic deletion and promoter hypermethylation causes underexpression of PTPRK mRNA in NKTCL, and methylation of PTPRK promoter significantly correlates with higher IPI (p<0.001) and with inferior overall survival (p=0.049) in NKTCL patients treated with the steroid-dexamethasone, methotrexate, ifosfamide, L-asparaginase, and etoposide (SMILE) regimen. Altogether, our findings show that PTPRK underexpression leads to STAT3 activation and contributes to NKTCL pathogenesis and that methylation of the PTPRK promoter correlates with a severe clinical course and worse prognosis in NKTCL patients treated with the SMILE protocol.-
dc.languageeng-
dc.relation.ispartofAutumn Annual Meeting of the Japanese Society of Pathology-
dc.relation.ispartof第60回日本病理学会秋期特別総会-
dc.titleReceptor-type tyrosine-protein phosphatase kappa promoter hypermethylation correlates with unfavorable prognosis in nasal NK/T-cell lymphoma patients treated with SMILE regimen-
dc.typeConference_Paper-
dc.identifier.emailAu Yeung, RKH: rex.auyeung@hku.hk-
dc.identifier.emailChen, WYW: wywchen@hkucc.hku.hk-
dc.identifier.emailWong, KY: kywonga@hkucc.hku.hk-
dc.identifier.emailLoong, F: floong@hkucc.hku.hk-
dc.identifier.emailKwong, YL: ylkwong@hkucc.hku.hk-
dc.identifier.emailSrivastava, G: sgopesh@hkucc.hku.hk-
dc.identifier.authorityAu Yeung, RKH=rp01877-
dc.identifier.authorityKwong, YL=rp00358-
dc.identifier.authoritySrivastava, G=rp00365-
dc.identifier.hkuros245132-

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