Figure 4
Figure 4. EZN-2208 treatment recapitulates HIF-1α silencing. (A) Relative expression of the indicated genes in MEC-1 cells treated with the indicated doses of EZN-2208 as compared with untreated cells. Data represent mean values ± SEM of 3 independent experiments. (B) Increase of cell mortality of MEC-1 cells treated with the indicated doses of EZN-2208 with respect to basal cell death in untreated cells. Data are expressed as percentages and represent mean values ± SEM of 3 independent experiments. (C) Relative expression of the indicated genes in primary CLL B cells from 8 patients treated with the indicated doses of EZN-2208 as compared with untreated cells. Data represent mean values ± SEM (n = 8). (D) Increase of cell mortality of primary CLL B cells treated with the indicated doses of EZN-2208 with respect to basal cell death in NT cells. Data are expressed as percentages and represent mean values ± SEM (n = 8). (E) Spleen weight of Rag2−/−γc−/− mice injected with MEC-1 cells, treated with EZN-2208 at day 18 after leukemia challenge, and euthanized at the end of treatment (day 27). Data are expressed as mean values ± SEM (n = 6). (F) Histopathological evaluation of BM and spleen colonization of Rag2−/−γc−/− mice injected with MEC-1 cells, treated and euthanized as in panel E. Data represent organ involvement as evaluated by a certified pathologist and are expressed as mean values ± SEM (n = 6). (G) Analysis of annexin V+ MEC-1 cells in the BM and spleen of leukemic mice treated and euthanized as in panel E. Data are expressed as percentage of annexin V+ cells within CD19+ cells in the indicated organs (n = 6). (H) Graph of average number of microvessels per field (original magnification ×40) in spleen colonized by MEC-1 cells at the end of EZN-2208 treatment as in panel E. Data are represented as mean values ± SEM (n = 3). (I) Kaplan-Meier survival curve of Rag2−/−γc−/− mice injected with MEC-1 cells, treated with EZN-2208 at day 18 after leukemia challenge, and euthanized when terminally sick (untreated, n = 9; EZN-2208-treated animals, n = 7). Data are representative of 1 of 2 experiments with similar results.

EZN-2208 treatment recapitulates HIF-1α silencing. (A) Relative expression of the indicated genes in MEC-1 cells treated with the indicated doses of EZN-2208 as compared with untreated cells. Data represent mean values ± SEM of 3 independent experiments. (B) Increase of cell mortality of MEC-1 cells treated with the indicated doses of EZN-2208 with respect to basal cell death in untreated cells. Data are expressed as percentages and represent mean values ± SEM of 3 independent experiments. (C) Relative expression of the indicated genes in primary CLL B cells from 8 patients treated with the indicated doses of EZN-2208 as compared with untreated cells. Data represent mean values ± SEM (n = 8). (D) Increase of cell mortality of primary CLL B cells treated with the indicated doses of EZN-2208 with respect to basal cell death in NT cells. Data are expressed as percentages and represent mean values ± SEM (n = 8). (E) Spleen weight of Rag2−/−γc−/− mice injected with MEC-1 cells, treated with EZN-2208 at day 18 after leukemia challenge, and euthanized at the end of treatment (day 27). Data are expressed as mean values ± SEM (n = 6). (F) Histopathological evaluation of BM and spleen colonization of Rag2−/−γc−/− mice injected with MEC-1 cells, treated and euthanized as in panel E. Data represent organ involvement as evaluated by a certified pathologist and are expressed as mean values ± SEM (n = 6). (G) Analysis of annexin V+ MEC-1 cells in the BM and spleen of leukemic mice treated and euthanized as in panel E. Data are expressed as percentage of annexin V+ cells within CD19+ cells in the indicated organs (n = 6). (H) Graph of average number of microvessels per field (original magnification ×40) in spleen colonized by MEC-1 cells at the end of EZN-2208 treatment as in panel E. Data are represented as mean values ± SEM (n = 3). (I) Kaplan-Meier survival curve of Rag2−/−γc−/− mice injected with MEC-1 cells, treated with EZN-2208 at day 18 after leukemia challenge, and euthanized when terminally sick (untreated, n = 9; EZN-2208-treated animals, n = 7). Data are representative of 1 of 2 experiments with similar results.

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