Data from: Characterization of leukemia-inducing genes using a proto-oncogene/homeobox gene retroviral human cDNA library in a mouse in vivo model

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.