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.
References
37
Referenced
78
10.1046/j.1365-2141.1996.d01-1468.x
10.1073/pnas.90.16.7784
10.1182/blood.V86.1.1.bloodjournal8611
10.1038/sj.leu.2400880
10.1016/S0092-8674(00)81389-6
10.1016/S0092-8674(00)80986-1
10.1073/pnas.88.23.10431
10.1016/S0046-8177(87)80002-3
10.1073/pnas.92.11.4917
10.1182/blood.V86.11.4263.bloodjournal86114263
10.1126/science.8351518
10.1128/mcb.8.1.301-308.1988
10.1016/S0092-8674(88)91175-0
10.1073/pnas.91.9.4004
10.1073/pnas.93.4.1642
- M Kurokawa, S Ogawa, T Tanaka, K Mitani, Y Yazaki, O N Witte, H Hirai Oncogene 11, 833–840 (1995). / Oncogene by Kurokawa M (1995)
10.1073/pnas.93.3.1044
10.1038/sj.onc.1202459
- M Kurokawa, T Tanaka, K Tanaka, S Ogawa, K Mitani, Y Yazaki, H Hirai Oncogene 12, 883–892 (1996). / Oncogene by Kurokawa M (1996)
10.1128/MCB.15.5.2383
10.1038/sj.leu.2401360
10.1128/mcb.12.1.183-189.1992
10.1016/S0092-8674(00)81388-4
10.1073/pnas.94.11.5697
10.1182/blood.V91.9.3134
10.1038/ng0397-303
10.1182/blood.V92.10.3829
10.1128/MCB.19.10.6918
- F Mitelman Catalog of Chromosomal Aberrations in Cancer (Wiley-Liss, New York), pp. 373–376 (1994). / Catalog of Chromosomal Aberrations in Cancer by Mitelman F (1994)
10.1073/pnas.95.20.11863
10.1073/pnas.90.14.6454
10.1182/blood.V92.10.3780
10.1084/jem.189.9.1399
- N Cascavilla, P Musto, G D'Arena, L Melillo, A M Carella, M P Petrilli, G Sanpaolo, M Carotenuto Haematologica 83, 392–397 (1998). / Haematologica by Cascavilla N (1998)
10.3109/10428199909083383
10.1182/blood.V92.2.596
10.1016/S0145-2126(98)00185-4
Dates
Type | When |
---|---|
Created | 23 years, 1 month ago (July 26, 2002, 10:37 a.m.) |
Deposited | 3 years, 4 months ago (April 12, 2022, 8:41 a.m.) |
Indexed | 4 months ago (May 4, 2025, 12:06 a.m.) |
Issued | 25 years, 7 months ago (Feb. 4, 2000) |
Published | 25 years, 7 months ago (Feb. 4, 2000) |
Published Online | 25 years, 7 months ago (Feb. 4, 2000) |
Published Print | 25 years, 6 months ago (Feb. 15, 2000) |
@article{Cuenco_2000, title={Human AML1/MDS1/EVI1 fusion protein induces an acute myelogenous leukemia (AML) in mice: A model for human AML}, volume={97}, ISSN={1091-6490}, url={http://dx.doi.org/10.1073/pnas.030421197}, DOI={10.1073/pnas.030421197}, number={4}, journal={Proceedings of the National Academy of Sciences}, publisher={Proceedings of the National Academy of Sciences}, author={Cuenco, Grace M. and Nucifora, Giuseppina and Ren, Ruibao}, year={2000}, month=feb, pages={1760–1765} }