Expression of NUP98/HHEX induces acute leukemia in mice. (A) Kaplan-Meier plot of primary recipients that received a transplant of NUP98/HHEX-transduced bone marrow cells (solid line, n = 10 average latency [285 ± 15 days]. Secondary recipients (dashed line, n = 10) succumbed to the disease with reduced latency (100 ± 20 days). Bone marrow transplantations have been done in 2 independent series. (B) Histology of representative primary mouse demonstrated the presence of leukemic blasts in blood smears and extensive leukemia tissue infiltration of organs including the spleen, liver, and lymph nodes. (C) Immunophenotyping of leukemic cells. Flow cytometric profiles of bone marrow–derived blasts of a representative NUP98/HHEX leukemia mouse. Infected cells are identified by EYFP⁺ fluorescence. (D) Expression of NUP98/HHEX fusion in spleen, bone marrow, and peripheral blood of 2 representative diseased mice was analyzed by RT-PCR analysis. (E) Viral integration analysis by Southern blotting of EcoRI-digested genomic DNA probed with an EYFP probe shows the clonal character of the disease. (F) Retroviral insertion sites in leukemic blasts from 4 mice with NUP98/HHEX-induced disease that underwent transplantation. Insertions were cloned using a splinkerette-PCR approach.