{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,29]],"date-time":"2026-09-29T20:28:58Z","timestamp":1790713738247,"version":"4.1.0"},"reference-count":23,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2017,5,8]],"date-time":"2017-05-08T00:00:00Z","timestamp":1494201600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Br J Haematol"],"published-print":{"date-parts":[[2017,9]]},"abstract":"Summary<\/jats:title>PTPN<\/jats:styled-content>6, a tyrosine phosphatase protein, plays a negative role in cell signal transduction and is negatively correlated with tumour formation and growth. However, epigenetic regulation mechanism of the PTPN<\/jats:styled-content>6<\/jats:italic> gene in advanced chronic myeloid leukaemia (CML<\/jats:styled-content>) remains unclear. This study investigated bone marrow or blood samples from 44 CML<\/jats:styled-content> patients and 10 healthy volunteers. KCL<\/jats:styled-content>22 and K562 cells were cultured and treated with demethylation drugs and histone deacetylase inhibitors. Real time quantitative polymerase chain reaction (qPCR<\/jats:styled-content>), methylation\u2010specific PCR<\/jats:styled-content>, bisulfite sequencing PCR<\/jats:styled-content>, Western blotting, co\u2010immunoprecipitation and chromatin immunoprecipitation (ChIP<\/jats:styled-content>) was performed. PTPN<\/jats:styled-content>6 was down\u2010regulated in cell lines and patients with advanced phase CML<\/jats:styled-content>, whereas DNMT<\/jats:styled-content>1, DNMT<\/jats:styled-content>3A, MECP<\/jats:styled-content>2, MBD<\/jats:styled-content>2 and HDAC<\/jats:styled-content>1 were up\u2010regulated. Treatment with 5\u2010azacytidine, decitabine, sodium valproate and LBH<\/jats:styled-content>589 increased PTPN<\/jats:styled-content>6 expression, but decreased that of DNMT<\/jats:styled-content>1, DNMT<\/jats:styled-content>3A, MECP<\/jats:styled-content>2, MBD<\/jats:styled-content>2 and HDAC<\/jats:styled-content>1. Immunoprecipitation and mass spectrometry showed that HDAC<\/jats:styled-content>1 combined directly with PTPN<\/jats:styled-content>6. ChIP<\/jats:styled-content>\u2010seq showed that HDAC<\/jats:styled-content>1 did not combine with the promoter region of PTPN<\/jats:styled-content>6<\/jats:italic>, while MAPK<\/jats:styled-content><\/jats:italic>, AKT<\/jats:styled-content><\/jats:italic>, STAT<\/jats:styled-content>5<\/jats:italic>, JAK<\/jats:styled-content>2<\/jats:italic> and MYC<\/jats:styled-content><\/jats:italic> promoter regions all combined with HDAC<\/jats:styled-content>1. PTPN<\/jats:styled-content>6 is associated with progression of CML<\/jats:styled-content>. Low expression level of PTPN<\/jats:styled-content>6 was associated with DNA<\/jats:styled-content> methylation and regulated by histone acetylation. HDAC<\/jats:styled-content>1 participates in the regulation of PTPN<\/jats:styled-content>6.<\/jats:p>","DOI":"10.1111\/bjh.14739","type":"journal-article","created":{"date-parts":[[2017,5,8]],"date-time":"2017-05-08T10:52:45Z","timestamp":1494240765000},"page":"728-738","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":22,"title":["Research on the epigenetic regulation mechanism of the PTPN<\/scp>6<\/i> gene in advanced chronic myeloid leukaemia"],"prefix":"10.1111","volume":"178","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-8359-5008","authenticated-orcid":false,"given":"Xiaokun","family":"Zhang","sequence":"first","affiliation":[{"name":"Department of Hematology The Second Hospital of Hebei Medical University Key Laboratory of Hematology Shijiazhuang Hebei China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lin","family":"Yang","sequence":"additional","affiliation":[{"name":"Department of Hematology The Second Hospital of Hebei Medical University Key Laboratory of Hematology Shijiazhuang Hebei China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaojun","family":"Liu","sequence":"additional","affiliation":[{"name":"Department of Hematology The Second Hospital of Hebei Medical University Key Laboratory of Hematology Shijiazhuang Hebei China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ziyuan","family":"Nie","sequence":"additional","affiliation":[{"name":"Department of Hematology The Second Hospital of Hebei Medical University Key Laboratory of Hematology Shijiazhuang Hebei China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xingzhe","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Hematology The Second Hospital of Hebei Medical University Key Laboratory of Hematology Shijiazhuang Hebei China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuxia","family":"Pan","sequence":"additional","affiliation":[{"name":"Department of Hematology The Second Hospital of Hebei Medical University Key Laboratory of Hematology Shijiazhuang Hebei China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jianmin","family":"Luo","sequence":"additional","affiliation":[{"name":"Department of Hematology The Second Hospital of Hebei Medical University Key Laboratory of Hematology Shijiazhuang Hebei 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