Oncotarget

Research Papers:

Eltrombopag and its iron chelating properties in pediatric acute myeloid leukemia

Maura Argenziano, Chiara Tortora, Alessandra Di Paola, Elvira Pota, Martina Di Martino, Daniela Di Pinto, Caterina Di Leva and Francesca Rossi _

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Oncotarget. 2021; 12:1377-1387. https://doi.org/10.18632/oncotarget.28000

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Abstract

Maura Argenziano1, Chiara Tortora1, Alessandra Di Paola2, Elvira Pota1, Martina Di Martino1, Daniela Di Pinto1, Caterina Di Leva1 and Francesca Rossi1

1 Department of Woman, Child and General and Specialist Surgery, University of Campania Luigi Vanvitelli, Naples 80138, Italy

2 Department of Experimental Medicine, University of Campania Luigi Vanvitelli, Naples 80138, Italy

Correspondence to:

Francesca Rossi,email: francescarossi@unicampania.it

Keywords: acute monocytic leukemia; eltrombopag; deferasirox; iron chelation; cancer

Received: May 10, 2021     Accepted: June 11, 2021     Published: July 06, 2021

Copyright: © 2021 Argenziano et al. This is an open access article distributed under the terms of the Creative Commons Attribution License (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

ABSTRACT

Pediatric acute myeloid leukemia (AML) represents 20% of total childhood leukemia diagnoses and is characterized by poor prognosis with a long-term survival rate around the 50%, when patients are properly treated. The standard treatment for pediatric AML currently consists in a combination of cytarabine (Ara-C) and antracycline. Iron plays an important role in cancer development and progression. Targeting iron and its metabolism mediators could be a novel therapeutic strategy in cancer.Deferasirox (DFX) inhibits cancer cell proliferation and its use as an antiblastic drug could be suggested. Eltrombopag (ELT), a thrombopoietin receptor agonist used in immunethrombocytopenia, shows anticancer properties related to its emerging iron chelating properties. We compare the anticancer effect of classically used cytarabine with DFX and ELT effects in a pediatric AML cell line, THP-1, in order to identify innovative and more effective therapeutic strategies. ELT and DFX reduce intracellular iron concentration by inhibiting its uptake and by promoting its release. In particular, even though further investigations are needed to better understand the extact underlying action mechanisms, we demonstrated that ELT improves cytarabine antineoplastic activity in pediatric AML cell line.


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