Can Iron Chelation Improve Outcomes in AML When Combined With Cytarabine?
Posted: Thursday, September 30, 2021
Maura Argenziano, MD, FACS, of the University of Campania Luigi Vanvitelli, Naples, Italy, and colleagues attempted to combine iron-chelating agents with standard leukemia therapy to see whether they could improve clinical outcomes in patients with acute myeloid leukemia (AML). This study, published in Oncotarget, demonstrates “promising synergism” between cytarabine and the thrombopoietin receptor agonist eltrombopag, specifically by halting proliferation and cell-cycle progression well as increasing apoptosis.
“On the other hand, we cannot confirm the effectiveness of [the iron chelator] deferasirox in AML, neither alone [nor] in combination with the classically used chemotherapy agent,” concluded the researchers. “Further investigations are certainly needed to clarify the exact mechanisms underlying the synergism between eltrombopag and cytarabine, in particular to understand whether eltrombopag’s iron-chelating properties are actually responsible for these anticancer activities.”
THP-1 infant AML cells were purchased from the American Type Culture Collection. Cells were harvested after 48 hours and subsequently washed and counted. In the event of 80% confluence, eltrombopag, deferasirox, and cytarabine were added alone and in combination to the cells. In addition, proteins from both non-treated and treated cells were extracted for Western blotting, and iron levels were measured from culture supernatants.
Cell viability remained unchanged with eltrombopag and deferasirox, although there was a notable decrease in viable cells treated with cytarabine. Also, when combined with eltrombopag, the cytotoxic effect of cytarabine was found to be intensified. There was a significant decrease in transferrin receptor 1 (TRF-1) and ferroportin, iron-binding proteins, in THP-1 cells treated with deferasirox; cells treated with eltrombopag alone or a combination with both iron chelators seemed to exhibit an increase in ferroportin. Of note, the researchers noted that all treatments reduced the expression level of nuclear factor kappa B, which is heavily involved in disease progression.
Disclosure: The study authors reported no conflicts of interest.