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

Cell. 1991 Aug 23;66(4):663-74. doi: 10.1016/0092-8674(91)90112-c.

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.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Amino Acid Sequence
  • Base Sequence
  • Blotting, Northern
  • Carrier Proteins / genetics*
  • Chromosomes, Human, Pair 15
  • Chromosomes, Human, Pair 17
  • DNA / genetics
  • DNA-Binding Proteins / genetics*
  • Gene Expression
  • Humans
  • Leukemia, Promyelocytic, Acute / genetics*
  • Molecular Sequence Data
  • Neoplasm Proteins*
  • Nuclear Proteins*
  • Oligonucleotides / chemistry
  • Oncogenes
  • Polymerase Chain Reaction
  • Promyelocytic Leukemia Protein
  • RNA, Messenger / genetics
  • Receptors, Retinoic Acid
  • Transcription Factors / genetics*
  • Transcriptional Activation
  • Translocation, Genetic
  • Tretinoin*
  • Tumor Suppressor Proteins

Substances

  • Carrier Proteins
  • DNA-Binding Proteins
  • Neoplasm Proteins
  • Nuclear Proteins
  • Oligonucleotides
  • Promyelocytic Leukemia Protein
  • RNA, Messenger
  • Receptors, Retinoic Acid
  • Transcription Factors
  • Tumor Suppressor Proteins
  • PML protein, human
  • Tretinoin
  • DNA

Associated data

  • GENBANK/M60962
  • GENBANK/M64383
  • GENBANK/M64384
  • GENBANK/M73778
  • GENBANK/M73779
  • GENBANK/M80185
  • GENBANK/S44816
  • GENBANK/S44821
  • GENBANK/S56137
  • GENBANK/S56139