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

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

Cancer Biol Ther. 2018 Mar 22;:1-39

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

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.

PMID: 29565710 [PubMed - as supplied by publisher]

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