AICA-riboside (acadesine), an activator of AMP-activated protein kinase with potential for application in hematologic malignancies.
BACKGROUND
Despite considerable advances, B-cell chronic lymphocytic leukemia (CLL) is incurable with standard approaches. Thus, there remains a need for new therapies, particularly for patients who develop chemoresistance to DNA-targeting treatments. AICA-riboside (acadesine) is a nucleoside with a wide range of metabolic effects, including release of adenosine and activation of AMP-activated protein kinase (AMPK), which was initially developed as a cardioprotective agent. More recently, it has been shown that AICA-riboside induces apoptosis in various models of leukemia, including CLL.


METHODS
The literature data show that apoptosis induced by AICA-riboside in CLL is not dependent on a functionally normal p53 pathway. Moreover, AICA-riboside is active towards resting and proliferative models of leukemia cells, including resistant phenotypes. Finally, studies in healthy subjects and during coronary artery bypass graft surgery show that AICA-riboside is devoid of serious toxicity.


RESULTS
This paper reviews the mechanisms of action of AICA-riboside in normal and malignant cells and discusses how AICA-riboside could impact CLL treatment.


CONCLUSIONS
We propose that AICA-riboside, which displays a relative selectivity and a favorable toxicity profile, may offer a new treatment option for CLL.
Van Den Neste
Eric
E
de Duve Institute, Université Catholique de Louvain, Laboratory of Physiological Chemistry, UCL 7539, Avenue Hippocrate 75, 1200 Brussels, Belgium. eric.vandenneste@uclouvain.be
Van den Berghe
Georges
G
Bontemps
Françoise
F
D055372:AMP-Activated Protein Kinases / Q000378:metabolism*; D000620:Aminoimidazole Carboxamide / Q000031:analogs & derivatives* / Q000494:pharmacology / Q000627:therapeutic use; D000818:Animals; D002986:Clinical Trials as Topic / Q000639:trends; D004789:Enzyme Activation / Q000187:drug effects / Q000502:physiology; D019337:Hematologic Neoplasms / Q000188:drug therapy* / Q000201:enzymology; D006801:Humans; D012263:Ribonucleosides / Q000494:pharmacology* / Q000627:therapeutic use*
D012263:Ribonucleosides; D000620:Aminoimidazole Carboxamide; C011651:acadesine; D055372:AMP-Activated Protein Kinases