Deletion of MBD2 inhibits proliferation of chronic myeloid leukaemia blast phase cells. Issue 8 (3rd August 2018)

• Record Type: Journal Article
• Authors: Cheng, Ling; Tang, Ying; Chen, Xing; Zhao, Lei; Liu, Songya; Ma, Yanna; Wang, Na; Zhou, Kuangguo; Zhou, Jianfeng; Zhou, Mi
• Is Part Of: Cancer biology & therapy. Volume 19:Issue 8(2018)
• Page Start: 676
• Page End: 686
• Publication Date: 2018-08-03
• Subjects: methyl-CpG-binding domain protein 2 -- DNA methylation -- chronic myeloid leukaemia -- blast crisis -- therapeutic target -- SHP1 -- JAK2/STAT3 pathway; 616.99406
• DOI: 10.1080/15384047.2018.1450113
• Languages: English
• ISSNs: 1538-4047

Abstract

ABSTRACT: Aberrant methylation of tumour suppressor genes is associated with the progression to a blast crisis in chronic myeloid leukaemia (CML). Methyl-CpG-binding domain protein 2 (MBD2) has been studied as a "reader" of DNA methylation in many cancers, but its role in CML is unclear. We constructed cell models of a homozygous deletion mutation of MBD2 using gene-editing technology in K562 cells and BV173 cells. Here, we demonstrated that the deletion of MBD2 inhibited cell proliferation capacity in vitro . MBD2 deletion also significantly inhibited K562 cell proliferation in a xenograft tumour model in vivo . Additionally, the JAK2/STAT3 signalling pathway, which is abnormally active in CML, was inhibited by MBD2 deletion, and MBD2 deletion could up-regulate the expression of SHP1. In conclusion, our findings suggest that MBD2 is a candidate therapeutic strategy for the CML blast phase.