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Chimeric Product of the Acute Promyelocytic Leukemia-specific t(15;17) Translocation
Cell Biology Section, Laboratory of Pulmonary Pathobiology, National Institute of Environmental Health Sciences, National Institutes of Health, Research Triangle Park, North Carolina 27709 [C. N., E. C. P., A. M. J.]; Istituto di Clinica Medica I, University Perugia, Policlinico Monteluce, 06100 Perugia, Italy [F. G., P. P. P., P. G. P.]; and Dipartimento di Biopatologia, Divisione di Ematologia, I University of Rome, 00161 Rome, Italy [F. L. C., G. A.]
The acute promyelocytic leukemia 15;17 chromosomal translocation fuses the PML gene to the RAR
locus. The resulting chimeric gene encodes for a putative PML-RAR fusion protein. PML is a putative transcriptional factor and RAR is one of the nuclear retinoic acid receptors through which retinoic acid regulates gene expression. In this study, we investigated the retinoid binding and biochemical properties of the PML-RAR protein by size exclusion high-performance liquid chromatography and immunoblot analysis and compared them with those of normal RAR. The introduction of the expression vector PSG5/PML-RAR into COS-1 cells led to high levels of expression of the PML-RAR fusion protein. This protein was primarily localized in the nucleus and bound retinoids with the same affinity and specificity as the wild type RAR receptor. The PML-RAR fusion protein, but not the RAR, was found in high molecular weight complexes with either itself or other nuclear factors. In the acute promyelocytic leukemia-derived cell line NB4, which contains the t(15;17) chromosomal marker, the PML-RAR product was also found as a high molecular complex. The interaction of the PML-RAR with itself or with other nuclear proteins may be important in understanding the role of the PML-RAR fusion protein in promyelocytic leukemogenesis.
1 Present address: Istituto di Istologia ed Embriologia Generale I, University of Rome, Via A. Scarpa 14, 00161 Rome, Italy.
2 To whom requests for reprints should be addressed, at NIEHS/NIH, P.O. Box 12233, Research Triangle Park, NC 27709.
Received 1/15/92. Accepted 4/20/92.
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