Mutations of the PML tumor suppressor gene in acute promyelocytic leukemia. Academic Article uri icon

Overview

abstract

  • The promyelocytic leukemia (PML) tumor suppressor of acute promyelocytic leukemia (APL) is essential for a number of proapoptotic and growth-suppressive pathways as well as for the activity of differentiating agents such as retinoic acid (RA). In human APL, the dose of PML is reduced to heterozygosity given that one allele is involved in the chromosomal translocation while the status of the remaining PML allele is unknown. We have therefore used single-strand conformational polymorphism (SSCP) and sequencing analysis to screen DNA from APL patients for mutations at the PML locus. We identified DNA sequence variations resulting in a truncated PML protein in APL cases that displayed RA resistance and a very poor prognosis. Mutation analysis also led to the identification of aberrant PML sequence variations in other hematopoietic malignancies. Complete functional loss of PML is therefore selected by the APL phenotype and associates with poor prognosis and RA unresponsiveness.

publication date

  • November 20, 2003

Research

keywords

  • Antineoplastic Agents
  • Leukemia, Promyelocytic, Acute
  • Neoplasm Proteins
  • Nuclear Proteins
  • Transcription Factors
  • Tretinoin

Identity

Scopus Document Identifier

  • 12144286886

Digital Object Identifier (DOI)

  • 10.1182/blood-2003-07-2200

PubMed ID

  • 14630830

Additional Document Info

volume

  • 103

issue

  • 6