Deferasirox reduces oxidative DNA damage in bone marrow cells from myelodysplastic patients and improves their differentiation capacity

• Published in: British journal of haematology Vol. 187; no. 1; pp. 93 - 104
• Main Authors: Jiménez‐Solas, Tamara, López‐Cadenas, Félix, Aires‐Mejía, Irene, Caballero‐Berrocal, Juan Carlos, Ortega, Rebeca, Redondo, Alba María, Sánchez‐Guijo, Fermín, Muntión, Sandra, García‐Martín, Luís, Albarrán, Beatriz, Alonso, José María, Del Cañizo, Consuelo, Hernández‐Hernández, Ángel, Díez‐Campelo, María
• Format: Journal Article
• Language: English
• Published: England Blackwell Publishing Ltd 01.10.2019
• Subjects: Bone marrow; Chelation; deferasirox; Deoxyribonucleic acid; DNA; DNA damage; Flow cytometry; Hematology; Intracellular; Iron; iron overload; Myelodysplastic syndrome; myelodysplastic syndromes; Oxidation; Oxidative stress; Reactive oxygen species; iron overload; deferasirox; DNA damage; myelodysplastic syndromes; reactive oxygen species
• ISSN: 0007-1048; 1365-2141
• DOI: 10.1111/bjh.16013

Summary Patients with low‐risk myelodysplastic syndromes (MDS) usually develop iron overload. This leads to a high level of oxidative stress in the bone marrow (BM) and increases haematopoietic cell dysfunction. Our objective was to analyse whether chelation with deferasirox (DFX) alleviates the consequences of oxidative stress and improves BM cell functionality. We analysed 13 iron‐overloaded MDS patients' samples before and 4–10 months after treatment with DFX. Using multiparametric flow cytometry analysis, we measured intracellular reactive oxygen species (ROS), DNA oxidation and double strand breaks. Haematopoietic differentiation capacity was analysed by colony‐forming unit (CFU) assays. Compared to healthy donors, MDS showed a higher level of intracellular ROS and DNA oxidative damage in BM cells. DNA oxidative damage decreased following DFX treatment. Furthermore, the clonogenic assays carried out before treatment suggest an impaired haematopoietic differentiation. DFX seems to improve this capacity, as illustrated by a decreased cluster/CFU ratio, which reached values similar to controls. We conclude that BM cells from MDS are subject to higher oxidative stress conditions and show an impaired haematopoietic differentiation. These adverse features seem to be partially rectified after DFX treatment.