Mml1, a new common integration site in murine leukemia virus-induced promonocytic leukemias maps to mouse chromosome 10.
MuLV-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-myb locus due to insertional mutagenesis, however, we also identified a number of leukemias that had proviral integrations in the absence of c-myb rearrangement 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-myb alterations. Chromosomal mapping studies, performed using progeny from interspecies backcross mice generated by mating (BALB/cAn x M. spretus)F1 females to BALB/cAN males, determined that Mml1 is located on the proximal end of mouse chromosome 10. Interestingly, there were no recombinants between c-myb and Mml1 in 101 backcross progeny and Mml1 was mapped approximately 20-25 kb upsteam of c-myb. Interestingly, c-myb mRNA 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 whether Mml1 integration prevents down regulation of c-myb expression or activates another gene on chromosome 10.
Koller
R
R
Laboratory of Genetics, National Cancer Institute, Bethesda, Maryland 20892, USA.
Krall
M
M
Mock
B
B
Bies
J
J
Nazarov
V
V
Wolff
L
L
D016475:3T3 Cells; D000818:Animals; D001665:Binding Sites; D002874:Chromosome Mapping; D003001:Cloning, Molecular; D005260:Female; D015870:Gene Expression; D015321:Gene Rearrangement; D009052:Leukemia Virus, Murine / Q000235:genetics*; D007942:Leukemia, Experimental / Q000235:genetics / Q000821:virology*; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008811:Mice, Inbred DBA; D016254:Mutagenesis, Insertional; D011518:Proto-Oncogene Proteins / Q000235:genetics; D020598:Proto-Oncogene Proteins c-myb; D011533:Proviruses / Q000235:genetics; D012192:Retroviridae Infections / Q000235:genetics / Q000821:virology*; D015534:Trans-Activators / Q000235:genetics; D014407:Tumor Cells, Cultured; D014412:Tumor Virus Infections / Q000235:genetics / Q000821:virology*; D016662:Virus Integration
D011518:Proto-Oncogene Proteins; D020598:Proto-Oncogene Proteins c-myb; D015534:Trans-Activators