Iron Overload Alters the Energy Metabolism in Patients With Myelodysplastic Syndromes: Results From the Multicenter FISM BIOFER Study

Myelodysplastic syndromes Myelodysplastic syndromes: (my-eh-lo-diss-PLASS-tik SIN-dromez) A group of disorders where the bone marrow does not work well, and the bone marrow cells fail to make enough healthy blood cells. Myelo refers to the bone marrow. Dysplastic means abnormal growth or development. People with MDS have low blood cell count for at… (MDS) are hematological malignancies characterized by ineffective hematopoiesis hematopoiesis: (hi-mat-uh-poy-EE-suss) The process of making blood cells in the bone marrow. and increased apoptosis apoptosis: Programmed cell death. in the bone marrow bone marrow: The soft, spongy tissue inside most bones. Blood cells are formed in the bone marrow. , which cause peripheral cytopenia cytopenia: (sie-tuh-PEE-nee-uh) A shortage of one or more blood cell types. Also called a low blood count. . Mitochondria are key regulators of apoptosis and a site of iron accumulation that favors reactive oxygen species (ROS) production with detrimental effects on cell survival. Although the energy metabolism could represent an attractive therapeutic target, it was poorly investigated in MDS. The purpose of the study was to analyze how the presence of myelodysplastic hematopoiesis, iron overload iron overload: A condition that occurs when too much iron accumulates in the body. Bone marrow failure disease patients who need regular red blood cell transfusions are at risk for iron overload. Organ damage can occur if iron overload is not treated. and chelation impact on mitochondrial metabolism. We compared energy balance, OxPhos activity and efficiency, lactic dehydrogenase activity and lipid peroxidation in mononuclear cells (MNCs), isolated from 38 MDS patients and 79 healthy controls. Our data show that ATP/AMP ratio is reduced during aging and even more in MDS due to a decreased OxPhos activity associated with an increment of lipid peroxidation. Moreover, the lactate fermentation enhancement was observed in MDS and elderly subjects, probably as an attempt to restore the energy balance. The biochemical alterations of MNCs from MDS patients have been partially restored by the in vitro iron chelation iron chelation: Iron chelation therapy is the main treatment used when you have a condition called iron overload. Iron overload means you have too much iron in your body. This can be a problem for people who get lots of red blood cell transfusions. Basics Red blood cells contain iron. Each time you get a… , while only slight effects were observed in the age-matched control samples. By contrast, the addition of iron chelators on MNCs from young healthy subjects determined a decrement in the OxPhos efficiency and an increment of lactate fermentation and lipid peroxidation. In summary, MDS-MNCs display an altered energy metabolism associated with increased oxidative stress, due to iron accumulation. This condition could be partially restored by iron chelation.