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| CHROMOSOMAL TRANSLOCATION T(15-17) IN HUMAN ACUTE PROMYELOCYTIC LEUKEMIA FUSES RAR-ALPHA WITH A NOVEL PUTATIVE TRANSCRIPTION FACTOR, PML |
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| Author(s): KAKIZUKA A, MILLER WH, UMESONO K, WARRELL RP, FRANKEL SR, MURTY VVVS, DMITROVSKY E, EVANS RM |
| Source: CELL Volume: 66 Issue: 4 Pages: 663-674 Published: AUG 23 1991 |
| Times Cited: 1,048 References: 65 |
| Abstract: A unique mRNA produced in leukemic cells from a t(15; 17) acute promyelocytic leukemia (APL) patient encodes a fusion protein between the retinoic acid receptor-alpha (RAR-alpha) and a myeloid gene product called PML. PML contains a cysteine-rich region present in a new family of apparent DNA-binding proteins that includes a regulator of the interleukin-2 receptor gene (Rpt-1) and the recombination-activating gene product (RAG-1). Accordingly, PML may represent a novel transcription factor or recombinase. The aberrant PML-RAR fusion product, while typically retinoic acid responsive, displays both cell type- and promoter-specific differences from the wild-type RAR-alpha. Because patients with APL can be induced into remission with high dose RA therapy, we propose that the nonliganded PML-RAR protein is a new class of dominant negative oncogene product. Treatment with RA would not only relieve this inhibition, but the activated PML-RAR protein may actually promote myelocyte differentiation. |
| Document Type: Article |
| Language: English |
| Reprint Address: KAKIZUKA, A (reprint author), SALK INST BIOL STUDIES, LA JOLLA, CA 92037 USA |
Addresses:
1. HOWARD HUGHES MED INST, LA JOLLA, CA 92037 USA
2. MEM SLOAN KETTERING CANC CTR, LEUKEMIA & DEV CHEMOTHERAPY SERV, NEW YORK, NY 10021 USA
3. MEM SLOAN KETTERING CANC CTR, MOLEC MED LAB, NEW YORK, NY 10021 USA
4. MEM SLOAN KETTERING CANC CTR, CANC GENET LAB, NEW YORK, NY 10021 USA |
| Publisher: CELL PRESS, 1050 MASSACHUSETTES AVE, CIRCULATION DEPT, CAMBRIDGE, MA 02138 |
| Subject Category: Biochemistry & Molecular Biology; Cell Biology |
| IDS Number: GC745 |
| ISSN: 0092-8674 |
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