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HPLC-based Assay to Monitor Extracellular Nucleotide/Nucleoside Metabolism in Human Chronic Lymphocytic Leukemia Cells
Published on: July 20, 2016
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
Importance Of The Field:
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.
Areas Covered In This Review:
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.
What The Reader Will Gain:
This paper reviews the mechanisms of action of AICA-riboside in normal and malignant cells and discusses how AICA-riboside could impact CLL treatment.
Take Home Message:
We propose that AICA-riboside, which displays a relative selectivity and a favorable toxicity profile, may offer a new treatment option for CLL.
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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