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Characterization of Leukemia-Inducing Genes Using a Proto-Oncogene/Homeobox Gene Retroviral Human cDNA Library in a Mouse In Vivo Model

Title
Characterization of Leukemia-Inducing Genes Using a Proto-Oncogene/Homeobox Gene Retroviral Human cDNA Library in a Mouse In Vivo Model
Author
정희용
Keywords
ACUTE MYELOID-LEUKEMIA; HEMATOPOIETIC STEM-CELLS; BONE-MARROW-CELLS; C-MYC; HOX GENES; EXPRESSION; MEIS1; MICE; MUTATIONS; TRANSFORMATION
Issue Date
2015-11
Publisher
PUBLIC LIBRARY SCIENCE
Citation
PLOS ONE, v. 10, NO 11, Page. 1-2
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 protooncogene 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.
URI
http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0143240http://hdl.handle.net/20.500.11754/28693
ISSN
1932-6203
DOI
10.1371/journal.pone.0143240
Appears in Collections:
COLLEGE OF MEDICINE[S](의과대학) > MEDICINE(의학과) > Articles
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