title: Characterization of Leukemia-Inducing Genes Using a Proto-Oncogene/Homeobox Gene Retroviral Human cDNA Library in a Mouse In Vivo Model.
abstract: The purpose of this research is to develop a method to screen a large number of potential driver mutations of acute myeloid leukemia (AML) using a retroviral cDNA library and murine bone marrow transduction-transplantation system. As a proof-of-concept, murine bone marrow (BM) cells were transduced with a retroviral cDNA library encoding well-characterized oncogenes and homeobox genes, and the virus-transduced cells were transplanted into lethally irradiated mice. The proto-oncogenes responsible for leukemia initiation were identified by PCR amplification of cDNA inserts from genomic DNA isolated from leukemic cells. In an initial screen of ten leukemic mice, the MYC proto-oncogene was detected in all the leukemic mice. Of ten leukemic mice, 3 (30%) had MYC as the only transgene, and seven mice (70%) had additional proto-oncogene inserts. We repeated the same experiment after removing MYC-related genes from the library to characterize additional leukemia-inducing gene combinations. Our second screen using the MYC-deleted proto-oncogene library confirmed MEIS1and the HOX family as cooperating oncogenes in leukemia pathogenesis. The model system we introduced in this study will be valuable in functionally screening novel combinations of genes for leukemogenic potential in vivo, and the system will help in the discovery of new targets for leukemia therapy.
authors.affiliation: Department of Biomedical Science, Graduate School of Biomedical Science and Engineering, Hanyang University, Seoul, Republic of Korea.
authors.forename: Su Hwa
authors.initials: SH
authors.lastname: Jang
authors.affiliation: Department of Biomedical Science, Graduate School of Biomedical Science and Engineering, Hanyang University, Seoul, Republic of Korea.
authors.forename: Sohyun
authors.initials: S
authors.lastname: Lee
authors.affiliation: Department of Biomedical Science, Graduate School of Biomedical Science and Engineering, Hanyang University, Seoul, Republic of Korea.
authors.forename: Hee Yong
authors.initials: HY
authors.lastname: Chung
mesh_terms: D000818:Animals; D001854:Bone Marrow Cells / Q000378:metabolism / Q000473:pathology; D016026:Bone Marrow Transplantation; D002460:Cell Line; D002471:Cell Transformation, Neoplastic / Q000235:genetics; D004195:Disease Models, Animal; D004843:Epistasis, Genetic; D005260:Female; D017353:Gene Deletion; D015870:Gene Expression; D015723:Gene Library; D005801:Genes, Homeobox; D005822:Genetic Vectors / Q000235:genetics; D016130:Immunophenotyping; D007938:Leukemia / Q000235:genetics* / Q000401:mortality / Q000473:pathology; D051379:Mice; D005810:Multigene Family; D000090063:Proto-Oncogene Mas; D016271:Proto-Oncogene Proteins c-myc / Q000235:genetics; D011519:Proto-Oncogenes; D012190:Retroviridae / Q000235:genetics; D014161:Transduction, Genetic
chemical_list: C000715470:MAS1 protein, human; D000090063:Proto-Oncogene Mas; D016271:Proto-Oncogene Proteins c-myc