Two strikes lead to leukemia

New genetic mapping studies explain why a certain mouse strain is predisposed to developing fatal leukemia. Turcotte et al., reporting on page 881, identify a point mutation in the transcription factor IRF-8 (interferon regulatory factor 8) that abolishes its function and sets the stage for a second, leukemia-triggering mutation.

The recombinant mouse strain BXH-2 is known to develop first a myeloproliferative disease characterized by enlarged spleens with excess granulocytes, and later a spontaneous, fatal myeloid leukemia. The myeloproliferative disease is associated with a mutation at the Myls locus on chromosome 8, and the leukemia with insertion of an endogenous murine leukemia virus (MuLV) into host tumor suppressor genes.

The offending virus arises from a recombination event between two innocuous MuLV proviruses; they are carried in the genome of BXH...