Transcriptomic changes induced by allosteric inhibitor RMC-4550 in FLT3 and KIT mutant human AML cell lines

Targeting the MAPK signaling is an effective therapeutic approach in acute myeloid leukemia (AML) with mutations in FLT3 and KIT tyrosine kinase receptors. SHP2 is a central node in the MAPK signaling pathway and SHP2 inhibition was shown to supress leukemia proliferation in vitro and in vivo. In order to investigate the gene expression alterations induced by allosteric SHP2 inhibition and identify potential co-targets for pharmacological inhibition, we treated three human FLT3 and KIT mutant AML cell lines with RMC-4550 and performed RNAseq. Differential gene expression analysis from RNA-seq in Molm-14, MV4-11 and SKNO-1 treated with RMC-4550 vs treated with vehicle