Fig. 1: Continuous HDAC6 inhibition increases survival of lymphoma-prone MYC-overexpressing mice.

A Western Blot analysis of Eµ-Myc lymphoma cells isolated from malignant lymph nodes and treated ex vivo with increasing concentrations of M-100 for 24 h. Levels of Myc were quantified to untreated conditions. Actin was used as a loading control. Cl. - cleaved. B Western Blot analysis of splenocytes from wild-type mice treated once via i.p. injection with 30 mg/kg M-100 or vehicle for the indicated time. Each lane represents one individual mouse. Vinculin was used as a loading control. Ac-tub - acetylated tubulin. C Survival curves of Eµ-Myc mice treated every 72 h with 30 mg/kg M-100 (n = 17) or vehicle (n = 15). Treatment (Tx) started at age 70 d for six weeks. Mice were monitored for additional six weeks for signs of lymphoma development. Median survival vehicle cohort: 136 d, M-100 cohort: not possible to calculate, untreated Eµ-Myc mice: 140 d. Log-Rank-test. D Lymphoma phenotypes of diseased Eµ-Myc mice measured by flow cytometry. E Spleen weights of all mice from the different cohorts. Spleen weights from wild-type mice serve as control. Wilcoxon rank-sum test. F Flow cytometry analysis of splenic immune cell populations of survivors. Unpaired Student’s t-test, two-tailed. G Survival curves of Eµ-Myc mice suffering from lymphoma treated with M-100 (median 16 d) or left untreated (median 6 d). Mice received M-100 (30 mg/kg) every 72 h starting when palpable lymph node swelling was present. Treatment continued until endpoint criteria were reached. Log-Rank-test. Data in A are representative of n = 3 independent experiments. E, F Each dot represents one mouse. Bars depict mean.