Arsenic treatment of acute promyelocytic leukemia affects neutrophil function in a compensatory manner

Abstract

Abstract Background Arsenic (ATO) and retinoic acid (ATRA) are successfully used as chemotherapy-free regimens to treat acute APL. Compared to traditional chemotherapy approaches, this therapy evokes fewer haematological side effects, such as severe neutropenia and thrombocytopenia, but little is known about the impact of the treatment on neutrophil function. Methods We included three patients undergoing consolidation treatment for APL. To evaluate the functionality of neutrophils, we assessed chemotaxis, ROS production, and neutrophil extracellular trap (NET) release during different time points of the treatment and compared them with neutrophils from healthy donors. Results We revealed that the chemotactic ability of neutrophils isolated from APL patients was decreased before starting each cycle of treatment. However, there was an increase in chemotactic ability in the first week of treatment compared to other time points. Additionally, we observed increased ROS production at the start of the treatment cycle. In vitro exposure of isolated neutrophils from healthy donors to ATO led to decreased chemotaxis at high ATO concentrations exceeding those achieved in vivo, while ROS production was not affected. Chemotaxis and ROS production were not altered by exposure to ATRA in vitro and neither ATO nor ATRA had an effect on neutrophils’ ability to release NETs. Conclusions Our study suggests that ATO and ATRA therapy alter neutrophil function by increasing chemotaxis and reducing ROS production. The effect on neutrophil function does not, however, seem to impact infection susceptibility in our patients, indicating that the enhanced functionality might compensate for the lowered neutrophil count.

Keywords

• Acute promyelocytic leukemia
• Neutrophils
• Chemotaxis
• Arsenic
• Infection risk assessment