Alterations of organotypic structures in cS5-transplanted mice and cS5 serine mutants. (A) At 8 weeks after BM transplantation, histopathologic analysis of PB, liver, spleen, and BM revealed signs of leukemia in cS5-transplanted mice, including elevated numbers of myeloid and lymphoid cells in the PB and disruption of spleen germinal center architecture with concomitant splenomegaly. In addition, the liver portal tracts and parts of the liver parenchyma in these mice were diffusely infiltrated by hematopoietic cells. Blast-like cells were detected in the BM. Contrary, mice transplanted with cS5 serine mutants did not show any abnormalities and histologically resembled the GFP vector controls. (B) At 32 weeks after transplantation, mice transplanted with cS5 single-serine mutants showed increased numbers of lymphoid cells in PB, with cS5-S725A–transplanted mice displaying a stronger phenotype characterized by disruption of the splenic architecture and infiltration of the liver by hematopoietic cells. cS5-SASA–transplanted mice did not show any signs of disease throughout the period of analysis. For each transplant group, a minimum of 8 mice was analyzed, which all displayed similar histologic features (magnifications: spleen ×100, liver ×200, BM and blood smear ×400).