Fig. 5
Reduction of C/EBPα p42/p30 ratio suppresses BCL2 and induces Venetoclax resistance by up-regulating DDIT3. A Quantitative PCR revealed that the mRNA level of CEBPA in AML cell lines was positively correlated with BCL2, but negatively correlated with BCL2L1 and MCL1. B The protein levels of BCL2, BCL-XL, and MCL1 in AML cell lines by western immunoblotting analysis. C-D The sensitivity to venetoclax cytotoxicity was positively relevant to the mRNA (C) and protein (D) levels of CEBPA in AML cell lines. E The protein level of MCL1 was significantly increased in THP-1 cells with CEBPA knockdown. F Compared with the negative control group, THP-1 cells with CEBPA knockdown showed significantly decreased apoptosis rate induced by venetoclax (5 μM, 48 h). G-H The protein levels of BCL2 were significantly reduced in NB4 cells (G) and THP-1 cells (H) with induction of C/EBPα-p30. I Compared with the negative control group, NB4 cells with induction of C/EBPα-p42 showed significantly increased apoptosis rate induced by venetoclax (5 μM, 48 h), while cells with induction of C/EBPα-p30 showed significantly decreased apoptosis rate. J Compared with the negative control group, THP-1 cells with induction of C/EBPα-p30 showed significantly decreased apoptosis rate induced by venetoclax (5 μM, 48 h). Data represent Mean ± SD (n = 3); *P < 0.05; **P < 0.01, ***P < 0.001