title: Large-scale identification of disease genes involved in acute myeloid leukemia.
abstract: Acute myeloid leukemia (AML) is a heterogeneous group of diseases in which chromosomal aberrations, small insertions or deletions, or point mutations in certain genes have profound consequences for prognosis. However, the majority of AML patients present without currently known genetic defects. Retroviral insertion mutagenesis in mice has become a powerful tool for identifying new disease genes involved in the pathogenesis of leukemia and lymphoma. Here we have used the Graffi-1.4 strain of murine leukemia virus, which causes predominantly AML, in a screen to identify novel genes involved in the pathogenesis of this disease. We report 79 candidate disease genes in common integration sites (CISs) and 15 genes whose family members previously were found to be affected in other studies. The majority of the identified sequences (60%) were not found in lymphomas and monocytic leukemias in previous screens, suggesting a specific involvement in AML. Although most of the virus integrations occurred in or near the 5' or 3' ends of the genes, suggesting deregulation of gene expression as a consequence of virus integration, 18 CISs were located exclusively within the genes, conceivably causing gene disruption.
authors.affiliation: Department of Hematology, Erasmus Medical Center, Rotterdam, The Netherlands.
authors.forename: Stefan J
authors.initials: SJ
authors.lastname: Erkeland
authors.forename: Marijke
authors.initials: M
authors.lastname: Valkhof
authors.forename: Claudia
authors.initials: C
authors.lastname: Heijmans-Antonissen
authors.forename: Antoinette
authors.initials: A
authors.lastname: van Hoven-Beijen
authors.forename: Ruud
authors.initials: R
authors.lastname: Delwel
authors.forename: Mirjam H A
authors.initials: MH
authors.lastname: Hermans
authors.forename: Ivo P
authors.initials: IP
authors.lastname: Touw
mesh_terms: D000208:Acute Disease; D000818:Animals; D000831:Animals, Newborn; D009052:Leukemia Virus, Murine / Q000472:pathogenicity*; D007942:Leukemia, Experimental / Q000235:genetics / Q000503:physiopathology / Q000821:virology; D007951:Leukemia, Myeloid / Q000235:genetics* / Q000503:physiopathology; D051379:Mice; D016254:Mutagenesis, Insertional; D011506:Proteins / Q000235:genetics*; D011533:Proviruses / Q000235:genetics; D012192:Retroviridae Infections / Q000821:virology; D017422:Sequence Analysis, DNA; D014412:Tumor Virus Infections / Q000821:virology; D016662:Virus Integration
chemical_list: D011506:Proteins