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

• DOI: 10.1111/bjh.16013
• Publication Date: 2019-06-07T01:48:07Z
• Authors: Tamara Jiménez‐Solas; Félix López‐Cadenas; Irene Aires‐Mejía; Juan Carlos Cabal...; Rebeca Ortega; Alba María Redondo; Fermín Sánchez‐Guijo; Sandra Muntión; Luís García‐Martín; Beatriz Albarrán; José María Alonso; Consuelo Del Cañizo; Ángel Hernández‐H...; María Díez‐Campelo
• Keywords: Adult; células madre; Iron Overload; Adolescent; humanos; estudios de casos y controles; Myelodysplastic syndromes; Bone Marrow Cells; síndromes mielodisplásicos; oxidación-reducción; Iron Chelating Agents; Young Adult; 03 medical and health sciences; 0302 clinical medicine; estudios prospectivos; Iron overload; Humans; Prospective Studies; Aged; Aged, 80 and over; daño del ADN; Stem Cells; sobrecarga de hierro; especies reactivas de oxígeno; células de la médula ósea; Cell Differentiation; Middle Aged; 3. Good health; Deferasirox; Oxidative Stress; diferenciación celular; estrés oxidativo; Case-Control Studies; Myelodysplastic Syndromes; quelantes del hierro; DNA damage; Reactive oxygen species; Reactive Oxygen Species; Oxidation-Reduction; DNA Damage

SummaryPatients 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.