Mechanistic effects of arsenic trioxide on acute promyelocytic leukemia and other types of leukemias

Acute promyelocytic leukemia (APL), a subtype of acute myeloid leukemia characterized with a translocation between promyelocytic leukemia gene (PML) on chromosome 15 and retinoic acid receptor alpha gene (RAR alpha) on chromosome 17. Transcription of this fusion gene results in PML/RAR alpha fusion protein blocking expression of critical genes involved in differentiation of myeloid cells through interaction with RAR element. PML/RAR alpha fusion protein prevents normal function of PML and RAR alpha as well as inhibiting apoptosis. Arsenic trioxide (ATO) is an important agent for the treatment of relapsed and newly diagnosed APL. ATO induces apoptosis, autophagy, and partial cellular differentiation as well as inhibiting cell growth and angiogenesis. Recognition of signaling pathways and molecular mechanisms induced by ATO can be effective for discovering novel treatment strategies to target leukemia cells. Also, it can be developed for the treatment of a variety of cancer cells. This review provides a perspective on anticancerous effects of ATO on APL and leukemia cells.

Automated summary

Acute promyelocytic leukemia (APL) is a subtype of acute myeloid leukemia characterized by translocation between specific genes. Arsenic trioxide (ATO) is an important treatment agent for APL, inducing apoptosis, autophagy, differentiation, and inhibiting cell growth and angiogenesis. Understanding the effects of ATO on signaling pathways can lead to novel treatment strategies for leukemia and other cancer cells.