MuLV-insertional mutagenesis of c-myb and Mml1 in a murine model for promonocytic leukemia.
Analysis of retroviral integration sites in MuLV-induced promonocytic leukemias has determined that two genetic loci, c-myb and Mml1, can contribute to disease development but not in the same leukemia. Recent studies aimed at understanding the function of Myb in leukemia development have focused on the consequences of ectopic Myb expression on monocytic and granulocytic differentiation in vitro. In all instances Myb was shown to block growth arrest but not commitment to differentiation, a result which is consistent with observed effects of Myb in leukemia development. No effect of Myb protein truncation was observed in these studies although similar truncations are produced as a result of insertional mutagenesis. Common integration site, Mml1, was recently identified and mapped to mouse chromosome 10 within 1cM of c-myb. Despite its linkage to c-myb, Myb mRNA and protein expression appear to be unaffected in leukemias with Mml1 integrations.
Bies
J
J
Laboratory of Genetics, National Cancer Institute, Bethesda, MD 20892-4255, USA.
Koller
R
R
Hoffman
B
B
Amanullah
A
A
Mock
B
B
Wolff
L
L
D000818:Animals; D002454:Cell Differentiation; D002460:Cell Line; D002874:Chromosome Mapping; D004195:Disease Models, Animal; D006098:Granulocytes / Q000166:cytology; D009052:Leukemia Virus, Murine / Q000235:genetics*; D007951:Leukemia, Myeloid / Q000235:genetics* / Q000821:virology*; D008264:Macrophages / Q000166:cytology; D051379:Mice; D009000:Monocytes / Q000166:cytology; D016254:Mutagenesis, Insertional; D011518:Proto-Oncogene Proteins / Q000096:biosynthesis / Q000235:genetics*; D020598:Proto-Oncogene Proteins c-myb; D011519:Proto-Oncogenes; D015534:Trans-Activators / Q000096:biosynthesis / Q000235:genetics*; D016662:Virus Integration
D011518:Proto-Oncogene Proteins; D020598:Proto-Oncogene Proteins c-myb; D015534:Trans-Activators