From Iron Chelation to Overload as a Therapeutic Strategy to Induce Ferroptosis in Leukemic Cells

Eric Grignano; Rudy Birsen; Nicolas Chapuis; Didier Bouscary

doi:10.3389/fonc.2020.586530

From Iron Chelation to Overload as a Therapeutic Strategy to Induce Ferroptosis in Leukemic Cells

Front Oncol. 2020 Sep 18:10:586530. doi: 10.3389/fonc.2020.586530. eCollection 2020.

Authors

Eric Grignano^{1

2}, Rudy Birsen^{1

2}, Nicolas Chapuis^{1

3}, Didier Bouscary^{1

2}

Affiliations

¹ Université de Paris, Institut Cochin, CNRS UMR8104, INSERM U1016, Paris, France.
² Assistance Publique-Hôpitaux de Paris, Centre-Université de Paris, Service d'Hématologie clinique, Hôpital Cochin, Paris, France.
³ Assistance Publique-Hôpitaux de Paris, Centre-Université de Paris, Service d'Hématologie biologique, Hôpital Cochin, Paris, France.

Abstract

Despite its crucial importance in numerous physiological processes, iron also causes oxidative stress and damage which can promote the growth and proliferation of leukemic cells. Iron metabolism is strictly regulated and the related therapeutic approaches to date have been to restrict iron availability to tumor cells. However, since a new form of iron-catalyzed cell death has been described, termed ferroptosis, and subsequently better understood, iron excess is thought to represent an opportunity to selectively kill leukemic cells and spare normal hematopoietic cells, based on their differential iron needs. This review summarizes the physiology of iron metabolism and its deregulation in leukemia, the known ferrotoposis pathways, and therapeutic strategies to target the altered iron metabolism in leukemia for the purposes of initiating ferroptosis in these cancer cells.

Keywords: acute myeloid leukemia; ferritinophagy; ferroptosis; iron; reactive oxygen species.

Publication types

Review