Retinoic acid receptor alpha in acute promyelocytic leukaemia

Cancer Surv. 1992:14:195-203.

Abstract

Acute promyelocytic leukaemia has two highly specific particularities: a t(15;17) chromosomal translocation and the ability of a differentiation inducer all-trans-RA, to revert the malignant phenotype both in vitro and in vivo. Molecular characterization of the t(15;17) translocation has shown that it fuses a previously unknown zinc finger encoding gene, PML, to the RAR alpha, suggesting a link between the molecular mechanism of transformation and of RA dependent differentiation. The PML/RAR alpha fusion receptor--which is functionally altered--may block RA target genes, impair RA mediated differentiation and lead to transformation. Alternatively, or in addition, the PML transduction pathway may also be affected. Although it is clear that RA treatment must relieve APL cells from differentiation arrest, so far no model can satisfactorily account for this effect.

Publication types

  • Review

MeSH terms

  • Carrier Proteins / physiology*
  • Cell Transformation, Neoplastic
  • Chromosomes, Human, Pair 15
  • Chromosomes, Human, Pair 17
  • Genes / physiology
  • Humans
  • Leukemia, Promyelocytic, Acute / etiology*
  • Leukemia, Promyelocytic, Acute / genetics
  • Neoplasm Proteins / physiology*
  • Nuclear Proteins*
  • Promyelocytic Leukemia Protein
  • Receptors, Retinoic Acid
  • Transcription Factors / physiology
  • Translocation, Genetic
  • Tretinoin
  • Tumor Suppressor Proteins

Substances

  • Carrier Proteins
  • Neoplasm Proteins
  • Nuclear Proteins
  • Promyelocytic Leukemia Protein
  • Receptors, Retinoic Acid
  • Transcription Factors
  • Tumor Suppressor Proteins
  • PML protein, human
  • Tretinoin