Abstract: Objective To study the expression and function of RNA methylation reader YTHDF2 in the development of human acute myeloid leukemia (AML). Methods The peripheral blood mononuclear cells (PBMCs) isolated from AML patients and normal controls were used to detect the relative expression of YTHDF2 mRNA by quantitative RT-PCR analysis; THP-1 cells were transfected with siRNAs specific to YTHDF2 or control. The effects of YTHDF2 knock-down on THP-1 cell proliferation were examined by CCK-8 (p<0.05). The effects of YTHDF2 knock-down on THP-1 cell monocytic differentiation were examined by FACS analysis. The influence of YTHDF2 on target gene MZF1 mRNA stability was determined by quantitative RT-PCR after AcD treatment. The influence of YTHDF2 on target gene MZF1 protein expression was determined by Western blot (p<0.05). Results The expression of YTHDF2 mRNA was up-regulated in the PBMCs from AML patients compared to the normal controls. Knock-down of YTHDF2 reduces THP-1 cell proliferation and promotes its monocytic differentiation induced by PMA. YTHDF2 could regulate MZF1 expression by affecting the stability of MZF1 mRNA. Conclusions YTHDF2 might act as oncogene in AML by controlling the expression of its target gene MZF1.

Key words: YTHDF2, RNA methylation, MZF1, acute myeloid leukemia