Mml1,a New Common Integration Site in Murine Leukemia Virus-Induced Promonocytic Leukemias Maps to Mouse Chromosome 10

AbstractMuLV-induced myeloid leukemias (MML) having promonocytic characteristics are produced with high incidence in some strains of adult mice that are undergoing chronic peritoneal inflammation. Previously we showed that many leukemias have rearrangements of the c-myblocus due to insertional mutagenesis, however, we also identified a number of leukemias that had proviral integrations in the absence of c-mybrearrangement. In the present study, a new locus,Mml1,was found to be a target of insertional mutagenesis in 10 of the promonocytic leukemias that lacked c-mybalterations. Chromosomal mapping studies, performed using progeny from interspecies backcross mice generated by mating (BALB/cAn ×M. spretus)F1females to BALB/cAN males, determined thatMml1is located on the proximal end of mouse chromosome 10. Interestingly, there were no recombinants between c-mybandMml1in 101 backcross progeny andMml1was mapped approximately 20–25 kb upsteam ofc-myb.Interestingly, c-mybmRNA and Myb protein are expressed at levels similar to the levels observed in myeloid progenitor cells, but are not overexpressed. It is anticipated that future experiments will determine whetherMml1integration prevents down regulation of c-mybexpression or activates another gene on chromosome 10