AICA-riboside (acadesine), an activator of AMP-activated protein kinase with potential for application in hematologic

Eric Van Den Neste1, Georges Van den Berghe, Françoise Bontemps

  • 1de Duve Institute, Université Catholique de Louvain, Laboratory of Physiological Chemistry, UCL 7539, Avenue Hippocrate 75, 1200 Brussels, Belgium. eric.vandenneste@uclouvain.be

Abstract

Insights

AICA-riboside shows promise as a novel therapy for chronic lymphocytic leukemia (CLL), effectively inducing apoptosis in leukemia cells, including chemoresistant types, with minimal toxicity.

Area of Science:

  • Oncology
  • Hematology
  • Pharmacology

Background:

  • Chronic lymphocytic leukemia (CLL) remains incurable with current treatments.
  • Chemoresistance to DNA-targeting therapies necessitates novel treatment strategies.
  • AICA-riboside (acadesine) exhibits anti-leukemic properties, including in CLL models.

Purpose of the Study:

  • To review the mechanisms of AICA-riboside action in normal and malignant cells.
  • To explore the potential of AICA-riboside as a new therapeutic option for CLL.

Main Methods:

  • Literature review of AICA-riboside's effects on leukemia cells.
  • Analysis of AICA-riboside's mechanism of action, including p53-independent apoptosis induction.
  • Evaluation of toxicity data from studies in healthy subjects and surgical patients.

Main Results:

  • AICA-riboside induces apoptosis in CLL cells, irrespective of p53 pathway status.
  • The compound is effective against both resting and proliferative leukemia cells, including resistant phenotypes.
  • AICA-riboside demonstrates a favorable toxicity profile in clinical studies.

Conclusions:

  • AICA-riboside exhibits relative selectivity and low toxicity.
  • This agent presents a potential new treatment avenue for CLL patients, particularly those with chemoresistance.

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