SUMOylation inhibitors compromise the growth and survival of Myc-driven lymphoma. (A) AA and 2-D08 are recently identified pharmacologic SUMOi that block SUMOylation of RanGap1. Immunoblot analyses of HEK293T cells treated with AA (top). Immunoblot analyses of Eµ-Myc lymphoma cells treated with 2-D08 (bottom). (B) Three different Eµ-Myc lymphoma cell lines were incubated with 50 µM AA (left) or 75 µM 2-D08 (right) and were counted at the indicated intervals (n = 3). Cell count was normalized to that of untreated control cells for each time point. (C) Cell death (sub-G1 cell fraction determined PI staining) following treatment with AA (left panel) or 2-D08 (right panel) (n = 3). (D) Primary Eµ-Myc lymphoma cells were treated with the indicated dose of AA or 2-D08. Annexin-V/fluorescence-activated cell sorter analyses was used to assess apoptosis. A representative experiment is shown. (E) Human BL cell lines were incubated with 50 µM AA and counted at the intervals indicated. Cell count was normalized to untreated controls for each time point (n = 3). (F) Human BL cell lines were treated with 50 µM AA for 48 hours and assessed by PI flow cytometry for DNA content (n = 3). DMSO, dimethylsulfoxide.