Survival and disease phenotype in mice that received a transplant of p210BCR/ABL- and/or FHZfp423-expressing BM cells. (A) Schematic structures of the retroviruses and the illustration of the experimental procedure. BM cells infected with p210BCR/ABL-expressing retrovirus (pMyIG/p210BCR/ABL), FHZfp423-expressing retrovirus (pMyIKO/FHZfp423), or both types of viruses were subjected to the BMT assay. KO indicates Kusabira Orange. (B) Acceleration of disease onset and altered disease phenotype by cotransduction of Zfp423 and p210BCR/ABL. In the top panel, survival curves of mice reconstituted with BM cells transduced with control retrovirus (control, n = 5), pMyIKO/FHZfp423 (FHZfp423, n = 10), pMyIG/p210BCR/ABL (p210BCR/ABL, n = 9), and both viruses (p210BCR/ABL+FHZfp423, n = 10) are shown as thin dotted, thick dotted, thin continuous, and thick continuous lines, respectively. In the bottom panel, the percentages of samples diagnosed as CML, B-ALL, and AML are shown by black, white, and shaded boxes, respectively. (C) Representative results of pathologic analysis of CML and B-ALL developed in mice transduced with p210BCR/ABL and p210BCR/ABL+FHZfp423, respectively. In the BM smears, proliferation of differentiated myeloid cells is observed in the CML case (top left panel), whereas monotonous proliferation of immature lymphoid tumor cells is apparent in the B-ALL case (bottom left panel). Massive infiltration of leukemic cells is shown in the spleen and liver (middle and right panels). (D) Representative results of flow cytometric analysis of B-ALL developed in mice transduced with p210BCR/ABL and FHZfp423. Leukemic cells are positive for both GFP and KO (top panel), confirming that they were originated from hematopoietic progenitor cells infected with both p210BCR/ABL and FHZfp423. GFP-positive leukemic cells showed positive staining for B220, but are negative for Mac-1, Gr-1, and CD3 (middle and bottom panels).