DOI: 10.1073/pnas.94.6.2551. A<i>PMLRAR</i>α transgene initiates murine acute promyelocytic leukemia

APMLRARα transgene initiates murine acute promyelocytic leukemia

10.1073/pnas.94.6.2551

Crossref journal-article

Proceedings of the National Academy of Sciences

Proceedings of the National Academy of Sciences (341)

Abstract

The malignant cells of acute promyelocytic leukemia (APL) contain a reciprocal chromosomal translocation that fuses the promyelocytic leukemia gene (PML) with the retinoic acid receptor α gene (RARα). To test the hypothesis that the chimeraPMLRARα plays a role in leukemogenesis, we expressed aPMLRARα cDNA in myeloid cells of transgenic mice.PMLRARα transgenic mice exhibited impaired neutrophil maturation early in life, which progressed at a low frequency over the course of several months to overt APL. Both the preleukemic state and the leukemia could be transplanted to nontransgenic mice, and the transplanted preleukemia could progress to APL. The APL recapitulated features of the human disease, including a response to retinoic acid. Retinoic acid caused the leukemic cells to differentiatein vitroandin vivo, eliciting remissions of both the preleukemic state and APL in mice. Our results demonstrate thatPMLRARα impairs neutrophil differentiation and initiates the development of APL. The transgenic mice described here provide an apparently accurate model for human APL that includes clear evidence of tumor progression. The model should be useful for exploring the molecular pathogenesis of APL and the mechanisms of the therapeutic response to retinoic acid, as well as for preclinical studies of therapeutic regimens.

Bibliography

Brown, D., Kogan, S., Lagasse, E., Weissman, I., Alcalay, M., Pelicci, P. G., Atwater, S., & Bishop, J. M. (1997). APMLRARÎ± transgene initiates murine acute promyelocyticâleukemia. Proceedings of the National Academy of Sciences, 94(6), 2551â2556.

Authors 8

Diane Brown (first)
Scott Kogan (additional)
Eric Lagasse (additional)
Irving Weissman (additional)
Myriam Alcalay (additional)
Pier Giuseppe Pelicci (additional)
Susan Atwater (additional)
J. Michael Bishop (additional)

References 40 Referenced 387

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M E Huang, Y C Ye, S R Chen, J C Zhao, L J Gu, J R Cai, L Zhao, J X Xie, Z X Shen, Z Y Wang Chin Med J (Engl) 100, 949–953 (1987). / Chin Med J (Engl) by Huang M E (1987)
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P Rousselot, B Hardas, A Patel, F Guidez, J Gaken, S Castaigne, A Dejean, H de The, L Degos, F Farzaneh, C Chomienne Oncogene 9, 545–551 (1994). / Oncogene by Rousselot P (1994)
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Dates

Type	When
Created	23 years, 1 month ago (July 26, 2002, 10:44 a.m.)
Deposited	2 years, 4 months ago (April 22, 2023, 8:33 a.m.)
Indexed	1 month, 2 weeks ago (July 14, 2025, 11:43 p.m.)
Issued	28 years, 5 months ago (March 18, 1997)
Published	28 years, 5 months ago (March 18, 1997)
Published Online	28 years, 5 months ago (March 18, 1997)
Published Print	28 years, 5 months ago (March 18, 1997)

Funders 0

None

BibTeX

@article{Brown_1997, title={APMLRARα transgene initiates murine acute promyelocytic leukemia}, volume={94}, ISSN={1091-6490}, url={http://dx.doi.org/10.1073/pnas.94.6.2551}, DOI={10.1073/pnas.94.6.2551}, number={6}, journal={Proceedings of the National Academy of Sciences}, publisher={Proceedings of the National Academy of Sciences}, author={Brown, Diane and Kogan, Scott and Lagasse, Eric and Weissman, Irving and Alcalay, Myriam and Pelicci, Pier Giuseppe and Atwater, Susan and Bishop, J. Michael}, year={1997}, month=mar, pages={2551–2556} }

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