Fig. 5: Treatment with MB reduces chromatin accessibility, negatively enriches mRNA expression in MYC targets and translation gene sets, reduces protein expression in PD, FPD-MM leukemia stem cells and induced greater loss of viability in FPD-MM compared to FPD.

A PD germline mutant Runx1 FPD and FPD-MM cells were treated ex vivo with the indicated concentrations of MB for 96 h. Then, the percentage non-viable cells was determined by TOPRO-3 iodide staining and flow cytometry. B Global ATAC-Seq heat map and peak profile in PD, FPD-MM17 cells treated with 1000 nM MB for 24 h at peak +/− 5 kb resolution. C–E Primary FPD-MM18 cells were treated with 1000 nM of MB for 24 h and bulk RNA-Seq analysis was performed. Gene set enrichment analysis (GSEA) in MB-treated FPD-MM18 cells compared with HALLMARK and REACTOME pathway datasets. F Patient-derived FPD-MM18 cells were treated with 1000 nM of MB for 24 h. Cells were harvested and analyzed by CyTOF analysis utilized a cocktail of rare metal element-tagged antibodies. Leukemia stem cells were defined by high expression of CLL-1, CD117, and CD123 and low expression of CD244, CD86, and CD11b. Heat map shows the absolute fold-change of significantly altered protein expressions in the treated over control cells.