3 years ago

Research on the epigenetic regulation mechanism of the PTPN6 gene in advanced chronic myeloid leukaemia

Xingzhe Wang, Ziyuan Nie, Xiaojun Liu, Xiaokun Zhang, Yuxia Pan, Jianmin Luo, Lin Yang
PTPN6, 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 PTPN6 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. KCL22 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 (ChIP) was performed. PTPN6 was down-regulated in cell lines and patients with advanced phase CML, whereas DNMT1, DNMT3A, MECP2, MBD2 and HDAC1 were up-regulated. Treatment with 5-azacytidine, decitabine, sodium valproate and LBH589 increased PTPN6 expression, but decreased that of DNMT1, DNMT3A, MECP2, MBD2 and HDAC1. Immunoprecipitation and mass spectrometry showed that HDAC1 combined directly with PTPN6. ChIP-seq showed that HDAC1 did not combine with the promoter region of PTPN6, while MAPK, AKT, STAT5, JAK2 and MYC promoter regions all combined with HDAC1. PTPN6 is associated with progression of CML. Low expression level of PTPN6 was associated with DNA methylation and regulated by histone acetylation. HDAC1 participates in the regulation of PTPN6.

Publisher URL: http://onlinelibrary.wiley.com/resolve/doi

DOI: 10.1111/bjh.14739

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