Figure 6.
Figure 6. MLL-AF4 suppression diminishes leukemic engraftment. (A) Survival curves of SCID mice that received a transplant of SEM cells. Prior to transplantation, SEM cells were electroporated twice with the indicated siRNAs. Pretreatment with the MLL-AF4 siRNA siMA6 extended median survival and increased overall survival significantly compared with mock or control siRNA siMM pretreatment (P < .01 according to log-rank test). In each treatment arm, 8 mice received a transplant. (B) FACS analysis of bone marrow. Bone marrow cells of animals were stained with α-human CD45 antibody and analyzed by flow cytometry. siRNAs electroporated prior to transplantation are indicated. (C) Liver and spleen histologies. Original magnification × 200; scale bar, 50 μm. Mice that received a transplant of mock or siMM-pretreated cells were moribund at the time of analysis. The animal that received a transplant of siMA6-pretreated cells was killed 228 days after transplantation without any sign of leukemia-associated morbidity. (D) Comparison of spleen size. The siRNAs used for the electroporation are indicated on top. (E) Graphic representation of organ weights. Organ weights were normalized to whole body weight. Normalized liver and spleen weights of surviving animals of the siMA6 group were significantly smaller than those from the mock or siMM group (P < .05 and P < .001, respectively).

MLL-AF4 suppression diminishes leukemic engraftment. (A) Survival curves of SCID mice that received a transplant of SEM cells. Prior to transplantation, SEM cells were electroporated twice with the indicated siRNAs. Pretreatment with the MLL-AF4 siRNA siMA6 extended median survival and increased overall survival significantly compared with mock or control siRNA siMM pretreatment (P < .01 according to log-rank test). In each treatment arm, 8 mice received a transplant. (B) FACS analysis of bone marrow. Bone marrow cells of animals were stained with α-human CD45 antibody and analyzed by flow cytometry. siRNAs electroporated prior to transplantation are indicated. (C) Liver and spleen histologies. Original magnification × 200; scale bar, 50 μm. Mice that received a transplant of mock or siMM-pretreated cells were moribund at the time of analysis. The animal that received a transplant of siMA6-pretreated cells was killed 228 days after transplantation without any sign of leukemia-associated morbidity. (D) Comparison of spleen size. The siRNAs used for the electroporation are indicated on top. (E) Graphic representation of organ weights. Organ weights were normalized to whole body weight. Normalized liver and spleen weights of surviving animals of the siMA6 group were significantly smaller than those from the mock or siMM group (P < .05 and P < .001, respectively).

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