Fig. 3. Menin inhibitor treatment depletes H3K27 acetyl mark on chromatin, depletes mRNA expression of MYC, MEIS1, and FLT3 in cultured and primary AML blasts and depletes Menin, BCL2, and MLL target gene expression levels in phenotypically defined leukemia stem cells.

A IGV plots showing signal tag density of H3K27Ac ChIP-Seq at the MEIS1 and FLT3 gene in MOLM13 cells treated with SNDX-50469 for 16 h. Black arrows mark the direction of the coding sequence of each gene. Blue bars beneath the gene indicate significant, log2 fold-changes in signal tag density of H3K27Ac in SNDX-50469-treated cells compared to control cells. B–D MOLM13, OCI-AML3, and PD MLL-AF9, FLT3-TKD AML cells were treated with the indicated concentrations of SNDX-50469 for 16 h. Total RNA was isolated, and reverse transcribed. The resulting cDNAs were used for qPCR as shown. The expression of GAPDH served as the normalization control. E Patient-derived AML cells were treated with 1000 nM of SNDX-50469 for 16 h. Cells were harvested and analyzed by CyTOF analysis utilizing a cocktail of rare metal element-tagged antibodies. Leukemia stem cells were defined by high expression of CLEC12A, CD123, CD244, CD99, and CD33 but low expression of CD11b.