Figure 6.
MB1-47 shows AMPK-mediated antileukemic effects in mouse primary leukemias in vivo. (A) Schematic illustration of treatment with MB1-47–containing diet in leukemic mice in vivo for 3 consecutive days (detailed in “Methods”; n = 5). (B-D) Changes in leukemia burden after 3 days of MB1-47 treatment, as assessed by total spleen weight (B) or by flow cytometry detection of leukemic GFP+ cells in spleen (C) and bone marrow (D). Statistical significance (P) was determined by using the 1-tailed Student t test. *P < .05; ***P < .005. (E) Immunoblot analyses of cleaved PARP in leukemic spleens after 3 days of MB1-47 treatment. (F) Flow cytometry representation of cell-cycle analysis of T-ALL cells from leukemic spleens after 3 days of MB1-47 treatment. P values were calculated using 2-way ANOVA for multiple comparisons; ***P < .005. (G-H) Kaplan-Meier survival curves of mice harboring isogenic Pten+ (G) and Pten− (H) T-ALLs treated with an MB1-47–containing diet or a control diet. (I) Schematic illustration of bone marrow progenitor-retroviral transduction protocol for the generation and analysis of NOTCH1-induced Ampk-conditional knockout T-ALLs. (J) Kaplan-Meier survival curves of mice harboring Ampk+ and Ampk− isogenic leukemias treated with an MB1-47–containing diet or a control diet. P values in survival curves were calculated with the log-rank test; n = 10 mice per group. ***P < .005.

MB1-47 shows AMPK-mediated antileukemic effects in mouse primary leukemias in vivo. (A) Schematic illustration of treatment with MB1-47–containing diet in leukemic mice in vivo for 3 consecutive days (detailed in “Methods”; n = 5). (B-D) Changes in leukemia burden after 3 days of MB1-47 treatment, as assessed by total spleen weight (B) or by flow cytometry detection of leukemic GFP+ cells in spleen (C) and bone marrow (D). Statistical significance (P) was determined by using the 1-tailed Student t test. *P < .05; ***P < .005. (E) Immunoblot analyses of cleaved PARP in leukemic spleens after 3 days of MB1-47 treatment. (F) Flow cytometry representation of cell-cycle analysis of T-ALL cells from leukemic spleens after 3 days of MB1-47 treatment. P values were calculated using 2-way ANOVA for multiple comparisons; ***P < .005. (G-H) Kaplan-Meier survival curves of mice harboring isogenic Pten+ (G) and Pten (H) T-ALLs treated with an MB1-47–containing diet or a control diet. (I) Schematic illustration of bone marrow progenitor-retroviral transduction protocol for the generation and analysis of NOTCH1-induced Ampk-conditional knockout T-ALLs. (J) Kaplan-Meier survival curves of mice harboring Ampk+ and Ampk isogenic leukemias treated with an MB1-47–containing diet or a control diet. P values in survival curves were calculated with the log-rank test; n = 10 mice per group. ***P < .005.

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