Analysis of progression from CMML to acute leukemia. (A) Survival curves of MOL4070A-infected (left panel) and ENU-injected (right panel) control and CblQ367P mice. The time points of intraperitoneal administration (ip) of pIpC, MOL4070A, and ENU are indicated by arrows, and the diseased mice are numbered. (B) Pathological findings of the CblQ367P mice with acute transformation. Macroscopic appearance, abnormal PB cells, and representative results of flow cytometric analyses of AML (no. 3) and B-cell ALL (no. 8) samples are shown in the left, middle, and right panels, respectively. In the left panel, the enlarged spleen is indicated by an arrow. In the middle panel, Giemsa-stained PB smears are shown: panel 1, WBCs with abnormal nuclei, including a pseudo–Pelger-Huet anomaly (indicated by arrows); panel 2, hypersegmented neutrophils (indicated by arrows); and panels 3 and 4, giant platelets, erythrocytes with a Howell-Jolly body, and an apoptotic cell (indicated by arrows, arrowhead, and a white arrowhead, respectively). Scale bar: 10 μm. (C) Expression levels of CIS genes, Mecom (Evi1), Sfpi1 (PU.1), and Rassf2 in the tumor tissues. The results are shown relative to those of a control spleen (Ctrl). Tumors with virus integration in the corresponding CIS gene are indicated by vertical arrows. (D) Retrovirus-mediated transfer of Evi1. Experimental procedure, survival curves of recipient mice, and a representative result of the flow cytometric analysis of a leukemic mouse are shown in the upper left, lower left, and right panels, respectively. In the lower left panel, diseased mice in the CblQ367P + Evi1 group are numbered.
