Fig 2: Pharmacodynamic and antitumor effects of AG-270 in myeloma(A) Correlation plot between the CytoTRACE scores in pPCs and mPCs from asymptomatic or symptomatic populations with mean MAT2A expression. The correlation (R) was assessed using the Spearman test.(B) Barplot of the impact of MAT2A inhibition with AG-270 on stem-like cells defined by ALDH positivity (left) or as the SP (right) in ANBL-6 cells.(C) ROS levels in the setting of AG-270 treatment, with pyocyanin- and N-acetyl-L-cysteine-treated cells serving as positive and negative controls, respectively, in ANBL-6 cells.(D) Impact on viability of ANBL-6 cells simultaneously treated with AG-270 (1–4 μM) and bortezomib (2–8 nM) over 12–72 h as measured with WST-1.(E) Combinatorial effect of AG-270 and bortezomib analyzed using SynergyFinder.(F) Cohorts of Vκ∗MYC mice (n = 12 each) were treated daily for 4 weeks with vehicle or AG- 270 (200 mg/kg), followed by observation. Serum obtained at the indicated time points was separated by electrophoresis, and disease burden was measured by densitometry to determine the monoclonal (M) protein, represented as (M-protein [treatment or post-treatment]/albumin) – (M-protein [baseline]/albumin).(G) Body weight changes during and after treatment with AG-270.Error bars represent means ± SD from at least triplicate experiments. ∗ indicates p ≤ 0.05; ∗∗p ≤ 0.01; ∗∗∗p ≤ 0.001; ∗∗∗∗p ≤ 0.0001; and n.s. non-significant differences, as determined by the t test with Welch’s correction.