Purine nucleoside phosphorylase inhibition as a novel therapeutic approach for B-cell lymphoid malignancies. Review uri icon

Overview

MeSH

  • Clinical Trials, Phase I as Topic
  • Clinical Trials, Phase II as Topic
  • Deoxyguanine Nucleotides
  • Humans
  • Leukemia, Lymphocytic, Chronic, B-Cell

MeSH Major

  • Leukemia, B-Cell
  • Purine Nucleosides
  • Purine-Nucleoside Phosphorylase
  • Pyrimidinones

abstract

  • Purine nucleoside phosphorylase (PNP) catalyzes the reversible phosphorolysis of ribonucleosides and 2'-deoxyribonucleosides to their respective bases. Endogenous PNP deficiency leads to specific T-cell immunodeficiency, a genetic disease that has prompted the development of PNP inhibitors as potential therapies for T-cell-mediated diseases. PNP inhibition leads to the elevation of 2'-deoxyguanosine levels and accumulation of intracellular deoxyguanosine 5'-triphosphate, inducing cellular apoptosis. Forodesine is a highly potent, orally active, rationally designed PNP inhibitor that has shown activity in preclinical studies with malignant cells and clinical utility against T-cell acute lymphoblastic leukemia and cutaneous T-cell lymphoma. Additional preliminary findings support its use for the management of some B-cell malignancies.

publication date

  • December 2007

has subject area

  • Clinical Trials, Phase I as Topic
  • Clinical Trials, Phase II as Topic
  • Deoxyguanine Nucleotides
  • Humans
  • Leukemia, B-Cell
  • Leukemia, Lymphocytic, Chronic, B-Cell
  • Purine Nucleosides
  • Purine-Nucleoside Phosphorylase
  • Pyrimidinones

Research

keywords

  • Journal Article
  • Review

Identity

Language

  • eng

Digital Object Identifier (DOI)

  • 10.1053/j.seminoncol.2007.11.004

PubMed ID

  • 18086344

Additional Document Info

start page

  • S29

end page

  • S34

volume

  • 34

number

  • 6 Suppl 5