FKBP12^F36V degron facilitates rapid degradation of endogenous MECOM in AML cells. (A) Schematic illustrating the gene-editing strategy to knock in an FKBP12^F36V degron, 2xHA tag, and eGFP at the C-terminus of the endogenous MECOM locus in human MUTZ-3 AML cells. (B) GFP expression assessed by flow cytometry in CD34⁺ vs CD34^– MUTZ-3 MECOM-FKBP12^F36V cells. (C) Time course western blot analysis of MECOM protein levels in MUTZ-3 cells following treatment with dTAG^V-1 (5-25 nM) or dimethyl sulfoxide (DMSO). (D) Volcano plot showing changes in protein abundance in MUTZ-3 MECOM-FKBP12^F36V cells treated for 2 hours with 500 nM dTAG^V-1 vs DMSO as assessed by mass spectrometry. n = 3 independent replicates. (E) MECOM ChIP-seq of MUTZ-3 MECOM-FKBP12^F36V cells treated with 500 nM dTAG^V-1 vs DMSO (n = 3). Each row represents a single MECOM(HA)-bound peak. Heat map is centered on ChIP-peak summits ±500 bp. (F) Bivariate plot showing CD34 and CD14 expression levels in MUTZ-3 MECOM-FKBP12^F36V cells treated with 500 nM dTAG^V-1 vs DMSO. (G-H) Percentage of CD34⁺ and CD14⁺ cells as observed in panel F. n = 3 independent replicates. Mean and standard error of the mean (SEM) are shown. (I) Viable cell count by trypan blue exclusion of MUTZ-3 MECOM-FKBP12^F36V cells treated with 500 nM dTAG^V-1 vs DMSO. n = 3 independent replicates. Mean and SEM are shown. eGFP, enhanced green fluorescent protein; GAPDH, glyceraldehyde-3-phosphate dehydrogenase; kDA, kilodalton.