Inhibition factors of arsenic trioxide therapeutic effects in patients with acute promyelocytic leukemia.

OBJECTIVE: To summarize limitations involved in arsenic trioxide therapeutic effects in acute promyelocytic leukemia, because current studies show that some individuals of acute promyelocytic leukemia have relatively poor outcomes during treatment with arsenic trioxide. DATA SOURCES: Most relevant articles were included in the PubMed database between 2000 and 2013 with the keywords "acute promyelocytic leukemia," "arsenic trioxide," "thiol" or "methylation." In addition, a few older articles were also reviewed. STUDY SELECTION: Data and articles related to arsenic trioxide effect in acute promyelocytic leukemia treatment were selected and reviewed. We developed an overview of limitations associated with arsenic trioxide therapeutic effect. RESULTS: This review focuses on the researches about the arsenic trioxide therapeutic effect in acute promyelocytic leukemia and summarizes three mainly limitations which can influence the arsenic trioxide therapeutic effect to different degrees. First, with the combination of arsenic and glutathione the therapeutic effect and cytotoxicity decrease when glutathione concentration increases; second, arsenic methylation, stable arsenic methylation products weaken the apoptosis effect of arsenic trioxide in leukemia cells; third, gene mutations affect the sensitivity of tumor cells to arsenic trioxide and increase the resistance of leukemia cells to arsenic trioxide. CONCLUSIONS: The chief limitations are listed in the review. If we can exclude all of them, we can obtain a better therapeutic effect of arsenic trioxide in patients with acute promyelocytic leukemia.