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Figure 2 | Journal of Hematology & Oncology

Figure 2

From: HDM2 antagonist MI-219 (spiro-oxindole), but not Nutlin-3 (cis-imidazoline), regulates p53 through enhanced HDM2 autoubiquitination and degradation in human malignant B-cell lymphomas

Figure 2

Upregulation of p53 protein predicts efficacy and biological response to MI-219 in primary lymphoma cells. A) Western blots of the upregulation of p53 and its target proteins upon HDM2 inhibition after 24 h in primary lymphoma cells isolated from four patients. B) Box plots show the cumulative biostatistical analyses of p53 target protein expression levels to estimate response predictors to HDM2 SMIs in primary B-lymphocytes isolated from lymphoma patients (n = 10). Western blots for each patient (n = 10) for each drug, dose, and time point for each protein detected. Quantification of Western blot bands (relative density) was calculated using ImageJ and normalized to internal control (GAPDH). Fold increase or decrease was calculated by standardizing each treatment as a ratio to the control. MI-219 is statistically more effective than Nutlin-3 (p = 0.001) overall regardless of p53 target protein or time point when main effects for drug, concentration, protein and time were fitted without interactions. Upregulation of p53 was statistically greater upon exposure to MI-219 than for Nutlin-3 at 24 h for equivalent concentration; 2.5 μM [*p = 0.05]; 5.0 μM [***p = 0.02] and 10 μM [**p = 0.03] shown in Figure 2-Bb).

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