Genetic heterogeneity in acute myeloid leukemia: maximizing information flow from MuLV mutagenesis studies.
The study of myeloid leukemia induced by slow transforming murine leukemia viruses (MuLV) in the laboratory mouse has led to discovery of many important genes with critical roles in regulating the growth, death, lineage determination and development of hematopoietic precursor cells. This review provides an overview of the susceptible strains and virus isolates that cause acute myeloid leukemia (AML) in mice. In addition, newer methodologies, involving the use of the polymerase chain reaction, that have been used to identify cancer genes mutated by proviral insertion in mouse models, will be discussed. As cancer is a multi-gene disease, a system in which pairs of oncogenic mutations are classified as redundant, neutral or synergistic is described. The potential to combine MuLV mutagenesis with recent advances in mouse transgenesis in order to model specific forms of myeloid leukemia or genetic pathways common in human AML will be discussed. Finally, a general strategy for maximizing these genetically rich models to foster a better understanding of AML physiology and developing therapies is proposed.
Largaespada
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Department of Genetics, Cell Biology and Development, Institute of Human Genetics, and University of Minnesota Cancer Center, University of Minnesota, Minneapolis 55455, USA.
D000208:Acute Disease; D000818:Animals; D018070:Biological Specimen Banks; D003433:Crosses, Genetic; D004273:DNA, Neoplasm / Q000235:genetics; D016208:Databases, Factual; D020869:Gene Expression Profiling; D015973:Gene Expression Regulation, Leukemic; D015723:Gene Library; D018740:Genetic Heterogeneity; D020022:Genetic Predisposition to Disease; D006801:Humans; D009052:Leukemia Virus, Murine / Q000235:genetics / Q000302:isolation & purification / Q000472:pathogenicity*; D007942:Leukemia, Experimental / Q000235:genetics* / Q000473:pathology / Q000821:virology; D007951:Leukemia, Myeloid / Q000235:genetics* / Q000473:pathology / Q000821:virology; D051379:Mice; D008815:Mice, Inbred Strains / Q000235:genetics / Q000821:virology*; D008822:Mice, Transgenic; D016254:Mutagenesis, Insertional; D009857:Oncogenes; D016133:Polymerase Chain Reaction; D011519:Proto-Oncogenes; D011533:Proviruses / Q000235:genetics; D012192:Retroviridae Infections / Q000235:genetics* / Q000473:pathology / Q000821:virology; D019076:Transgenes; D014412:Tumor Virus Infections / Q000235:genetics* / Q000473:pathology / Q000821:virology
D004273:DNA, Neoplasm