Figure 4.
EAPB0503 effect on NPM1c post-translational modification is mediated through the SENP3 degradation and p14ARF upregulation. Western blot analysis of basal levels of NPM1c, SENP3, ARF in untreated OCI-AML3 and OCI-AML2 cells (A) and in blasts from NPM1c or wt-NPM1 AML patients (B). Western blot analysis of NPM1c, SENP3, ARF in EAPB0503 treated OCI-AML3 and OCI-AML2 cells for 6, 24 and 48 h (C). Histograms represent the densitometries of SENP3/Actin and ARF/H3 in 3 independent experiments. Western blot analysis of NPM1c, SENP3, ARF in blasts from patients with NPM1c (red) or wt-NPM1 (black) AML patients following ex vivo treatemnt with EAPB0503 for 6 h (D) or 24 h (E). Histograms represent the average densitometries of NPM1c/actin, SENP3/actin and ARF/H3 of the three NPM1c and three wt-NPM1 patients represented in the Western blots. *, ** and *** indicate p values ≤ 0.05; 0.01 and 0.001, respectively. P-values less than 0.05 were considered significant.