Understanding the Molecular Mechanisms Underlying Anemia in Myelodysplastic Syndromes: From Erythropoiesis to New Therapeutic Approaches

Minimizing the transfusion burden is one of the primary clinical goals for most patients with myelodysplastic syndromes (MDS), which are incurable hematopoietic stem cell neoplasms. In some patients, supportive red blood cell transfusions can lead to clinical improvement, but frequent transfusions induce iron overload, which can have detrimental effects on cardiac and hepatic function, affect patients' quality of life, and incur additional healthcare costs. In this review, we summarize how erythropoiesis is regulated under steady-state conditions, dissect the molecular mechanisms underlying anemia in MDS, and review therapeutic approaches to overcome ineffective erythropoiesis in patients with these diseases. SIGNIFICANCE: A better understanding of the biological mechanisms underlying anemia in MDS is needed to develop targeted therapies for a personalized treatment approach. Anemia, a hallmark of MDS, highly affects patients' quality of life and contributes to overall morbidity. Current knowledge of the mechanisms of action of the available drugs targeting anemia in MDS is limited.