Pluto Biosciences, Inc

GSE149049: Transcriptomic effects of combination Menin-MLL1 inhibition and FLT3 inhibition on human AML cells

Bulk RNA sequencing

Chromosomal translocations of the MLL1 gene cooccur with the activating mutations in FLT3 kinase in acute myeloid leukemia patients, providing the rationale to explore combination of the menin-MLL1 inhibitor (MI-3454) and FLT3 inhibitor (Gilteritinib) in leukemia models. Here, we pursued global gene expression studies after 7 days of treatment of MOLM13 cells (harboring MLL-AF9 and FLT3-ITD) with MI-3454 and Gilteritinib used as single agents and in combination. We observed that MYC, differentiation and stemness-associated gene programs were disrupted by the single agent treatments, but the effect was enhanced upon combinatorial treatment. These results provide a mechanistic input on the increased activity of MI-3454 when combined with Gilteritinib in leukemia models versus single agent treatment. SOURCE: James Ropa ( - Indiana University

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