Iron Overload, Oxidative Stress, and Somatic Mutations in MDS: What Is the Association?

Abstract

Introduction: Iron overload (IOL) accumulates in myelodysplastic syndromes (MDS) from expanded erythropoiesis and transfusions. Somatic mutations (SM) are frequent in MDS and stratify patient risk. MDS treatments reversing or limiting transfusion dependence are limited.

Methods: The literature was reviewed on how IOL and oxidative stress interact with specific SM in MDS to influence cellular physiology. PubMed searches included keywords of each specific mutation combined with iron, oxidative stress, and reactive oxygens species (ROS). Papers relevant to hematopoietic stem/progenitor cells, the bone marrow microenvironment, MDS, AML or other myeloid disorders were preferred. Included were the most frequent SM in MDS, SM of the International Prognostic Scoring System-Molecular (IPSS-M), of familial predisposing conditions and the CMML PSS-molecular.

Results: About 31 SM plus four familial conditions were searched. Discussed are the frequency of each SM, whether function is gained or lost, early or late SM status, a function of the unmutated gene, and function considering iron and oxidative stress.

Discussion: Given limited effective MDS therapies, considering how IOL and ROS interact with SM to influence cellular physiology in the hematopoietic system, increasing bone marrow failure progression or malignant transformation may be of benefit and support optimization of measures to reduce IOL or neutralize ROS.