NUP98-TOP1 expression induces a lethal leukemia. (A) Survival curve for mice that received transplants with CTL GFP-transduced cells (dashed line, n = 10) or NUP98-TOP1-transduced cells (solid line, n = 17, average latency 225 ± 56 days). Secondary recipients transplanted with 102 to 106 primary BM cells succumbed to disease with reduced latency (42-147 days). (B) Southern blot analysis of genomic DNA from primary mice reveals full-length proviral integration. DNA was digested with XbaI, which cuts once in each LTR. (C) Northern blot analysis of total RNA from NUP98-TOP1 mice. (D) Southern blot analysis reveals that NUP98-TOP1 induces monoclonal or oligoclonal disease, which is transplantable to secondary recipients. The labeling indicates the experiment number and the mouse used to transplant secondary recipients. Genomic DNA from moribund mice was digested with BglII (NUP98-TOP1) or EcoRI (NT-Y723F), which cut once in the provirus sequence. Membranes were hybridized with a probe specific to GFP. In panel D, 1° indicates primary; 2°, secondary.
