Fig. 2: FLT3-ITD AML exhibit marked sensitivity to RSK1 inhibition. | Blood Cancer Journal

Fig. 2: FLT3-ITD AML exhibit marked sensitivity to RSK1 inhibition.

From: RSK1 dependency in FLT3-ITD acute myeloid leukemia

Fig. 2

A FLT3 and RPS6KA1 KO gene dependency score across 26 AML cell lines from DepMap. B Bi-axial flow cytometry plots of apoptosis and necrosis markers in FLT3-ITD cell lines following RPS6KA1 knockdown. C PMD-026 sensitivity across a myeloid cell line panel representative of various driver mutations. Cells were treated across various PMD-026 concentrations for 96 h. N = 6 biological replicates. D Cell viability assays of MV4-11 and MOLM-13 cells treated across various inhibitor combinations for 96 h. E Immunoblot of MV4-11 and MOLM-13 cells treated with indicated doses of PMD-026 for 24 h. F Immunoblot after knockdown with two RPS6KA1 shRNAs or a non-targeting pLKO control. G Immunoblot of MV4-11 cells following 24 h treatment with inhibitors at the indicated concentrations. H Venn diagram of shared DEGs between PMD-026 and quizartinib treatment relative to DMSO control. Cells were treated in duplicate with 500 nM PMD-026 or 50 nM quizartinib for 24 h. I Enrichment dot plot of top altered Hallmark pathways from top 500 DEGs from (H). J Heatmap showing genes of interest from (H).

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