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Acute leukemia with promyelocytic features in PML/RARα transgenic mice
Open accessAbstract
Acute promyelocytic leukemia (APL) is associated with reciprocal chromosomal translocations involving the retinoic acid receptor α (RARα) locus on chromosome 17. In the majority of cases, RARα translocates and fuses with the promyelocytic leukemia (PML) gene located on chromosome 15. The resulting fusion genes encode the two structurally unique PML/RARα and RARα/PML fusion proteins as well as aberrant PML gene products, the respective pathogenetic roles of which have not been elucidated. We have generated transgenic mice in which the PML/RARα fusion protein is specifically expressed in the myeloid-promyelocytic lineage. During their first year of life, all the PML/RARα transgenic mice have an abnormal hematopoiesis that can best be described as a myeloproliferative disorder. Between 12 and 14 months of age, 10% of them develop a form of acute leukemia with a differentiation block at the promyelocytic stage that closely mimics human APL even in its response to retinoic acid. Our results are conclusive in vivo evidence that PML/RARα plays a crucial role in the pathogenesis of APL.
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Cited by
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Wang, Z.-G., Ruggero, D., Ronchetti, S., Zhong, S., Gaboli, M., Rivi, R., & Pandolfi, P. P. (1998) · Nature Genetics · doi:10.1038/3073 · Cited by 558
Self-citationRole of PML in Cell Growth and the Retinoic Acid Pathway
Gang Wang, Z., Delva, L., Gaboli, M., Rivi, R., Giorgio, M., Cordon-Cardo, C., Grosveld, F., & Paolo Pandolfi, P. (1998) · Science · doi:10.1126/science.279.5356.1547 · Cited by 517
Self-citationAcute promyelocytic leukaemia: novel insights into the mechanisms of cure
de Thé, H., & Chen, Z. (2010) · Nature Reviews Cancer · doi:10.1038/nrc2943 · Cited by 488
Yuan, Y., Zhou, L., Miyamoto, T., Iwasaki, H., Harakawa, N., Hetherington, C. J., Burel, S. A., Lagasse, E., Weissman, I. L., Akashi, K., et al. (2001) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.171321298 · Cited by 431
Survival of acute myeloid leukemia cells requires PI3 kinase activation
Xu, Q., Simpson, S.-E., Scialla, T. J., Bagg, A., & Carroll, M. (2003) · Blood · doi:10.1182/blood-2002-11-3429 · Cited by 394
Metadata
- Authors
- He, L.-Z., Tribioli, C., Rivi, R., Peruzzi, D., Pelicci, P. G., Soares, V., Cattoretti, G., & Pandolfi, P. P.
- Venue
- Proceedings of the National Academy of Sciences
- Published
- 1997-05-13
- Volume
- 94
- Issue
- 10
- Pages
- 5302-5307
- ISSN
- 0027-8424 (ISSN-L)
- 1091-6490
- OpenAlex
- W2012661561
- Cited by
- 339
- References
- 0
- FWCI
- 7.88
- Type
- journal article
- Language
- en
- Open access
- green
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- He, L.-Z., Tribioli, C., Rivi, R., Peruzzi, D., Pelicci, P. G., Soares, V., Cattoretti, G., & Pandolfi, P. P. (1997). Acute leukemia with promyelocytic features in PML/RARα transgenic mice. Proceedings of the National Academy of Sciences. https://doi.org/10.1073/pnas.94.10.5302
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