Cooperative activation of Hoxa and Pbx1-related genes in murine myeloid leukaemias.
Retroviruses induce myeloid leukaemia in BXH-2 mice by the insertional mutation of cellular proto-oncogenes or tumour suppressor genes. Disease genes can thus be identified by proviral tagging through the identification of common viral integration sites in BXH-2 leukaemia. Here, we describe a new approach for proviral tagging that greatly facilitates the identification of BXH-2 leukaemia genes. Using this approach, we identify three genes whose expression is activated by proviral integration in BXH-2 leukaemias; Hoxa7, Hoxa9, and a Pbx1-related homeobox gene, Meis1. Proviral activation of Hoxa7 or Hoxa9 is strongly correlated with proviral activation of Meis1 implying that Hoxa7 and Hoxa9 cooperate with Meis1 in leukaemia formation. These studies provide the first genetic evidence that Pbx1-related genes cooperate with Hox genes in leukaemia formation and identify a number of new murine myeloid leukaemia genes.
Nakamura
T
T
Mammalian Genetics Laboratory, NCI-Frederick Cancer Research and Development Center, Maryland 21702, USA.
Largaespada
D A
DA
Shaughnessy
J D
JD
Jenkins
N A
NA
Copeland
N G
NG
D000818:Animals; D002874:Chromosome Mapping; D003001:Cloning, Molecular / Q000379:methods; D018899:CpG Islands; D004268:DNA-Binding Proteins / Q000235:genetics*; D015252:Deoxyribonucleases, Type II Site-Specific; D004195:Disease Models, Animal; D005260:Female; D015972:Gene Expression Regulation, Neoplastic / Q000235:genetics*; D005801:Genes, Homeobox / Q000235:genetics / Q000502:physiology; D052138:Genes, Neoplasm / Q000235:genetics; D018398:Homeodomain Proteins / Q000235:genetics*; D007951:Leukemia, Myeloid / Q000235:genetics*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008815:Mice, Inbred Strains; D000075064:Myeloid Ecotropic Viral Integration Site 1 Protein; D009363:Neoplasm Proteins / Q000235:genetics*; D000075062:Pre-B-Cell Leukemia Transcription Factor 1; D011518:Proto-Oncogene Proteins / Q000235:genetics*; D011533:Proviruses / Q000235:genetics; D014775:Virus Activation; D016662:Virus Integration / Q000235:genetics
D004268:DNA-Binding Proteins; D018398:Homeodomain Proteins; C000616391:MEIS1 protein, human; C000616392:Meis1 protein, mouse; D000075064:Myeloid Ecotropic Viral Integration Site 1 Protein; D009363:Neoplasm Proteins; D000075062:Pre-B-Cell Leukemia Transcription Factor 1; D011518:Proto-Oncogene Proteins; C097899:homeobox protein HOXA9; C083400:PBX1 protein, human; C024408:endodeoxyribonuclease SacI; D015252:Deoxyribonucleases, Type II Site-Specific