Deletion of MBD2 inhibits proliferation of chronic myeloid leukaemia blast phase cells.

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.

journal_name

Cancer Biol Ther

journal_title

Cancer biology & therapy

authors

Cheng L,Tang Y,Chen X,Zhao L,Liu S,Ma Y,Wang N,Zhou K,Zhou J,Zhou M

doi

10.1080/15384047.2018.1450113

subject

Has Abstract

pub_date

2018-08-03 00:00:00

pages

676-686

issue

8

eissn

1538-4047

issn

1555-8576

journal_volume

19

pub_type

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