Expression data from MV4-11 cells after treatment with ATRA, NVP-BEZ235 or the combination of both drugs for 3h, 12h and 24h

Aberrant activity of the PI3K/AKT/mTOR (PAM) pathway as well as suppressed retinoic acid signaling contribute to enhanced proliferation and a block in differentiation of immature myeloid cells in AML Therefore, we sought to target MV4-11 cells by a combined strategy using small molecule inhibitors against members of the PAM signaling pathway in conjunction with all-trans retinoic acid (ATRA). A detailed analysis of transcriptome changes in MV4-11 cells revealed that NVP-BEZ235 and ATRA regulated the same biologic pathways, but acted on different gene sets within these pathways. Especially, we found a strong repression of MYC-target genes and genes involved in cellular programs such as cell cycle regulation, metabolism or differentiation. MV4-11 cells were treated with either 100 nM ATRA, 100 nM NVP-BEZ235, 100 nM ATRA + 100 nM NVP-BEZ235 or left untreated. Treatment was stopped 3h, 12h or 24h following treatment start and total RNA was isolated.