Strategies to inhibit arsenic trioxide-induced cardiotoxicity in acute promyelocytic leukemia.

OBJECTIVE

Arsenic trioxide (ATO) is a drug commonly used for the treatment of acute promyelocytic leukemia (APL). Although ATO has been shown to cause significant improvement in patients, it is associated with serious side effects, which sometimes lead to the patient's death. In this review paper, we examine the reports of ATO-induced cardiotoxicity in APL patients and evaluate the strategies to reduce the incidence of such toxicity.

METHODS

The key search terms were "arsenic trioxide," "acute promyelocytic leukemia," "cardiotoxicity," "molecular pathway," and "biomarker."

RESULTS

Studies have indicated the involvement of several molecular pathways in ATO-induced cardiotoxicity. These pathways increase the production of reactive oxygen species by interfering with intracellular calcium homeostasis as well as impairing the transfer of calcium into endoplasmic reticulum and mitochondria. On the other hand, increasing or decreasing expressions of some microRNAs (miRs) have been shown to play a role in cardiotoxicity.

CONCLUSION

Finally, it can be stated that given the essential role of molecular pathways in cardiotoxicity and considering the fact these pathways impair the regulation of miRs expression, identification of molecular pathways involved in ATO-induced cardiotoxicity aimed at targeting miRs could be a new therapeutic strategy to prevent cardiotoxicity.