Teriflunomide renewed DNMT1 depletion in HMA-resistant AML cells to a greater extent than venetoclax. (A) Teriflunomide renewed DNMT1 depletion in HMA-resistant THP1. Parental and HMA-resistant TP53-mutated AML cells (THP1) (HMA-resistant THP1 cultured continuously in indicated concentrations of decitabine and 5-azacytidine), were treated with venetoclax 2μM, teriflunomide 20μM with and without cytidine 100μM for 24 hours. Western blots at 24 hours. (B) Cell counts. Cell counts at 96 hours by automated counter. Independent experiments in triplicate. P values, paired 2-sided t test, for teriflunomide vs vehicle. (C) Apoptosis activation measured by flow cytometry for Annexin V staining. Mean ± SD, raw data in supplemental Figure 2. P values from paired 2-sided t tests, compared with vehicle. Independent experiments in triplicate. (D) CD11b expression. Flow cytometry, counts normalized to mode. Vehicle, venetoclax 2 μM, or teriflunomide 20μM treatment for 120 hours. (E) Giemsa-stained cytospin preparations. Treatments as per panel D. Leica Upright Microscope-Orion. Original magnification ×400; scale bar, 20 μm. 5Aza, 5-azacytidine; Cyt, cytidine; Dec, decitabine; Res, resistant; Teri, teriflunomide; Veh, vehicle; Ven, venetoclax; WB, Western blot.