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Research on the epigenetic regulation mechanism of the PTPN 6 gene in advanced chronic myeloid leukaemia
Author(s) -
Zhang Xiaokun,
Yang Lin,
Liu Xiaojun,
Nie Ziyuan,
Wang Xingzhe,
Pan Yuxia,
Luo Jianmin
Publication year - 2017
Publication title -
british journal of haematology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.907
H-Index - 186
eISSN - 1365-2141
pISSN - 0007-1048
DOI - 10.1111/bjh.14739
Subject(s) - chromatin immunoprecipitation , decitabine , hdac1 , cancer research , microbiology and biotechnology , dna methylation , biology , myeloid leukemia , azacitidine , bisulfite sequencing , histone , histone deacetylase , gene expression , promoter , biochemistry , gene
Summary PTPN 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 6 gene in advanced chronic myeloid leukaemia ( CML ) remains unclear. This study investigated bone marrow or blood samples from 44 CML patients and 10 healthy volunteers. KCL 22 and K562 cells were cultured and treated with demethylation drugs and histone deacetylase inhibitors. Real time quantitative polymerase chain reaction ( qPCR ), methylation‐specific PCR , bisulfite sequencing PCR , Western blotting, co‐immunoprecipitation and chromatin immunoprecipitation (Ch IP ) was performed. PTPN 6 was down‐regulated in cell lines and patients with advanced phase CML , whereas DNMT 1, DNMT 3A, MECP 2, MBD 2 and HDAC 1 were up‐regulated. Treatment with 5‐azacytidine, decitabine, sodium valproate and LBH 589 increased PTPN 6 expression, but decreased that of DNMT 1, DNMT 3A, MECP 2, MBD 2 and HDAC 1. Immunoprecipitation and mass spectrometry showed that HDAC 1 combined directly with PTPN 6. Ch IP ‐seq showed that HDAC 1 did not combine with the promoter region of PTPN 6 , while MAPK , AKT , STAT 5 , JAK 2 and MYC promoter regions all combined with HDAC 1. PTPN 6 is associated with progression of CML . Low expression level of PTPN 6 was associated with DNA methylation and regulated by histone acetylation. HDAC 1 participates in the regulation of PTPN 6.