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.

KEYWORDS:

• methyl-CpG-binding domain protein 2
• DNA methylation
• chronic myeloid leukaemia
• blast crisis
• therapeutic target
• SHP1
• JAK2/STAT3 pathway

Abbreviations

GAPDH	=	glyceraldehyde-3-phosphate dehydrogenase
MBD2	=	ethyl-CpG binding domain protein 2
JAK2	=	Janus kinase 2
STAT3	=	signal transducer and activator of transcription 3
c-Myc	=	MYC proto-oncogene, bHLH transcription factor
CCND1	=	Cyclin D1
Bcl-xL	=	B-cell lymphoma-extra large
SHP1	=	protein tyrosine phosphatase, non-receptor type 6.

Disclosure of potential conflicts of interest

No potential conflicts of interest were disclosed.

Additional information

Funding

This work was supported in part by the Key Program of the National Natural Science Foundation of China (JF Zhou, no. 81630006) and the General Program of NNSF of China (JF Zhou, no. 81570196)., the Youth Science Fund Project of NNSF of China (K Zhou, no. 81400122).