Finding a role for PML in APL pathogenesis: a critical assessment of potential PML activities

Leukemia. 2002 Oct;16(10):1906-17. doi: 10.1038/sj.leu.2402724.

Abstract

In normal mammalian cells the promyelocytic leukemia protein (PML) is primarily localized in multiprotein nuclear complexes called PML nuclear bodies. However, both PML and PML nuclear bodies are disrupted in acute promyelocytic leukemia (APL). The treatment of APL patients with all-trans retinoic acid (ATRA) results in clinical remission associated with blast cell differentiation and reformation of the PML nuclear bodies. These observations imply that the structural integrity of the PML nuclear body is critically important for normal cellular functions. Indeed, PML protein is a negative growth regulator capable of causing growth arrest in the G(1) phase of the cell cycle, transformation suppression, senescence and apoptosis. These PML-mediated, physiological effects can be readily demonstrated. However, a discrete biochemical and molecular model of PML function has yet to be defined. Upon first assessment of the current PML literature there appears to be a seemingly endless list of potential PML partner proteins implicating PML in a variety of regulatory mechanisms at every level of gene expression. The purpose of this review is to simplify this confusing field of research by using strict criteria to deduce which models of PML body function are well supported.

Publication types

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

MeSH terms

  • DNA Repair / physiology
  • DNA Replication / physiology
  • Gene Expression Regulation / physiology
  • Humans
  • Leukemia, Promyelocytic, Acute / physiopathology*
  • Neoplasm Proteins / physiology*
  • Nuclear Proteins*
  • Promyelocytic Leukemia Protein
  • RNA Processing, Post-Transcriptional / physiology
  • Transcription Factors / physiology*
  • Tumor Suppressor Proteins

Substances

  • Neoplasm Proteins
  • Nuclear Proteins
  • Promyelocytic Leukemia Protein
  • Transcription Factors
  • Tumor Suppressor Proteins
  • PML protein, human