Results of therapy with AAV8-IL24 in MLL/AF4 Tg mice. (A) Comparison of the results of immunohistopathologic analysis between one mouse from the AAV8-IL24 group and one mouse from the AAV8-EGFP group. Although CD45R/B220+ pro-B-cell lymphoma/leukemia infiltration (green fluorescence) was observed in the liver, lung, spleen, and BM in EGFP#1 (AAV-EGFP group), no lymphoma/leukemia infiltration was observed in IL24#1 (AAV-IL24 group). (B) Comparison of the results of FACS analysis of PB between 1 mouse from the AAV8-IL24 group and 1 mouse from the AAV8-EGFP group. FACS analysis showed that CD45R/B220+CD19+CD43+ leukemia cells accounted for 3.62% of WBC in IL24#1 (AAV-IL24 group), but only 0.86% of WBCs in EGFP#1 (AAV-EGFP group). (C) H&E-stained BM sections from MLL/AF4 Tg mice (AAV8-EGFP group vs AAV8-IL24 group). (D) Comparison of the number of microvessels in MLL/AF4 Tg mice (AAV8-EGFP group vs AAV8-IL24 group). The number of microvessels in MLL/AF4 Tg mice transduced with AAV8-IL24 was significantly decreased in comparison with MLL/AF4 Tg mice transduced with AAV8-EGFP (18.6 ± 6.1/mm2 vs 44.0 ± 4.0/mm2, P = .004). (E) WB analysis confirmed in vivo that up-regulated S100A6 and HOXA9 were inhibited and p53 acetylation, MEIS1, BiP, cleaved caspase 8, and cleaved caspase 3 were activated in the AAV8-IL24 group.
