Abstract
The human t(3;21)(q26;q22) translocation is found as a secondary mutation in some cases of chronic myelogenous leukemia during the blast phase and in therapy-related myelodysplasia and acute myelogenous leukemia. One result of this translocation is a fusion between the
AML1
,
MDS1
, and
EVI1
genes, which encodes a transcription factor of approximately 200 kDa. The role of the
AML1/MDS1/EVI1
(
AME
) fusion gene in leukemogenesis is largely unknown. In this study, we analyzed the effect of the
AME
fusion gene
in vivo
by expressing it in mouse bone marrow cells via retroviral transduction. We found that mice transplanted with
AME
-transduced bone marrow cells suffered from an acute myelogenous leukemia (AML) 5–13 mo after transplantation. The disease could be readily transferred into secondary recipients with a much shorter latency. Morphological analysis of peripheral blood and bone marrow smears demonstrated the presence of myeloid blast cells and differentiated but immature cells of both myelocytic and monocytic lineages. Cytochemical and flow cytometric analysis confirmed that these mice had a disease similar to the human acute myelomonocytic leukemia. This murine model for AME-induced AML will help dissect the molecular mechanism of AML and the molecular biology of the
AML1, MDS1,
and
EVI1
genes.