Chromosomal translocation t(15;17) in human acute promyelocytic leukemia fuses RARα with a novel putative transcription factor, PML Journal Article

  


Authors: Kakizuka, A.; Miller, W. H. Jr; Umesono, K.; Warrell, R. P. Jr; Frankel, S. R.; Murty, V. V. V. S.; Dmitrovsky, E.; Evans, R. M.
Article Title: Chromosomal translocation t(15;17) in human acute promyelocytic leukemia fuses RARα with a novel putative transcription factor, PML
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 α (RARα) 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 RARα. 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. © 1991.
Keywords: human cell; dna-binding proteins; case report; polymerase chain reaction; gene expression; transcription factor; transcription factors; oncogenes; leukemia, promyelocytic, acute; dna; amino acid sequence; molecular sequence data; rna, messenger; leukemia cell; carrier proteins; recombinant protein; acute myeloblastic leukemia; chromosome translocation; base sequence; blotting, northern; oligonucleotides; chromosomes, human, pair 17; chromosomes, human, pair 15; tretinoin; receptors, retinoic acid; trans-activation (genetics); human; priority journal; article; support, non-u.s. gov't; support, u.s. gov't, p.h.s.; translocation (genetics); retinoic acid binding protein
Journal Title: Cell
Volume: 66
Issue: 4
ISSN: 0092-8674
Publisher: Cell Press  
Date Published: 1991-08-23
Start Page: 663
End Page: 674
Language: English
DOI: 10.1016/0092-8674(91)90112-c
PUBMED: 1652368
PROVIDER: scopus
DOI/URL:

https://www.scopus.com/inward/record.uri?eid=2-s2.0-0025780876&doi=10.1016%2f0092-8674%2891%2990112-C&partnerID=40&md5=f575ff6f72ae0907792ad737df392593
Notes: Article -- Export Date: 27 September 2019 -- Source: Scopus
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MSK Authors
  1. Raymond P Warrell
    175 Warrell
  2. Ethan Dmitrovsky
    98 Dmitrovsky
  3. Vundavalli V. V. S. Murty
    53 Murty
  4. Wilson H. Miller Jr
    48 Miller
  5. Stanley R. Frankel
    13 Frankel
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