Abstract
RETINOIC acid is a vitamin A derivative with striking effects on development and cell differentiation1–3. Several nuclear retinoic acid receptors (RARs), acting as ligand-inducible transcription factors, have been characterized4–8 and indirect evidence suggests that they have distinct roles9–11. One of the most intriguing properties of retinoic acid is its ability to induce in vivo differentiation of acute promyelocytic leukaemia (APL) cells into mature granulocytes, leading to morphological complete remissions12–13. Because the RARα gene maps to chromosome 17q21 (ref. 14), close to the t(15;17) (q21–qll–22) translocation specifically associated with APL15, we analysed RARα gene structure and expression in APL cells. We report here that, in one APL-derived cell line, the RARα gene has been translocated to a locus, myl, on chromosome 15, resulting in the synthesis of a myl/RARα fusion messenger RNA. Using two probes located on either side of the cloned breakpoint, we have found genomic rearrangements of one or other locus in six patients out of eight, demonstrating that the RARα and/or myl genes are frequently rearranged in APL and the breakpoints are clustered. These findings strongly implicate retinoic acid receptor α in leukaemogenesis.
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References
Roberts, A. & Sporn, M. in The Retinoids (eds Sporn, M., Roberts, A. & Goodman, D.) 209–286 (Academic Press, Orlando, 1984).
Strickland, S. & Mahdavi, M. Cell 15, 393–403 (1978).
Thaller, C. & Eichete, G. Nature 327, 625–628 (1987).
Giguere, V., Ong, E. S., Segui, P. & Evans, R. M. Nature 330, 624–629 (1987).
Petkovich, M., Brand, N. J., Krust, A. & Chambon, P. Nature 330, 444–450 (1987).
de Thé, H., Marchio, A., Tiollais, P. & Dejean, A. Nature 330, 667–670 (1987).
Brand, N. et al. Nature 332, 850–853 (1988).
Zelent, A., Krust, A., Petkovich, M., Kastner, P. & Chambon, P. Nature 339, 714–717 (1989).
de Thé, H., Marchio, A., Tiollais, P. & Dejean, A. EMBO J. 8, 429–433 (1989).
Dollé, P. et al. Nature, 342, 702–705 (1989).
de Thé, H., Vivanco-Ruiz, M. D. M., Tiollais, P., Stunnenberg, H. & Dejean, A. Nature, 343, 177–180 (1990).
Huang, M. E. et al. Blood 72, 567–571 (1988).
Castaigne, S. et al. Blood (in the press).
Mattei, M. G., Petkovich, M., Mattei, J. F., Brand, N. & Chambon, P. Hum. Genet. 80, 186–187 (1988).
Larson, R. A. et al. Am. J. Med. 76, 827–841 (1984).
Claverie, J. M. & Bougueleret, L. Nucleic Acids Res. 14, 179–196 (1986).
Green, S. & Chambon, P. Nature 324, 615–617 (1986).
Sap, J., Munoz, A., Schmitt, J., Stunnenberg, H. & Vennström, B. Nature 340, 242–244 (1989).
Damm, K., Thompson, C. & Evans, R. Nature 339, 593–597 (1989).
Dejean, A., Bougueleret, L., Grzeschik, K. H. & Tiollais, P. Nature 322, 70–72 (1986).
Hollenberg, S., Guiguere, V., Segui, P. & Evans, R. Cell 49, 39–46 (1987).
Kumar, V. et al. Cell 51, 941–951 (1987).
Tora, L., Gronemeyer, H., Turcotte, B., Gaub, M. P. & Chambon, P. Nature 333, 185–188 (1988).
Green, S., Kumar, V., Theulaz, I., Wahli, W. & Chambon, P. EMBO J. 7, 3037–3044 (1988).
Saiki, R. et al. Science 239, 487–491 (1988).
Kawasaki, E. S. et al. Proc. natn. Acad. Sci. U.S.A. 85, 5698–5702 (1988).
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de Thé, H., Chomienne, C., Lanotte, M. et al. The t(15;17) translocation of acute promyelocytic leukaemia fuses the retinoic acid receptor α gene to a novel transcribed locus. Nature 347, 558–561 (1990). https://doi.org/10.1038/347558a0
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DOI: https://doi.org/10.1038/347558a0
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