Metabolomic Investigation of Myelodysplastic Syndromes, Multiple Myeloma, and Homozygous β-Thalassemia

Chronic anemia is commonly diagnosed in older adults and serves an important indicator of both reactive and clonal conditions. Many underlying diseases, such as myelodysplastic syndromes and multiple myeloma, are more prevalent amongst the elderly, while novel therapeutic approaches have transformed pediatric disorders of poor prognosis, such as beta-thalassemia, to a chronic disease of older adults. Thus, the increasing prevalence of chronic anemia in older ages is largely attributed to more frequent diagnostic and therapeutic evaluations and demographic changes. The etiology of anemia in adults is complex, ranging from genetic mutations to bone marrow failure syndromes, chronic kidney disease, nutritional deficiencies, and inflammatory processes, while in some cases no clear etiology is found. For this reason, extensive research is ongoing to introduce novel therapeutic targets and improve quality of life. Management of anemia in adults depends on severity and especially on the underlying conditions of each patient. Metabolic pathway analyses have revealed alterations in various pathways, including glycolysis, pyruvate, propanoate, glycerophospholipid, galactose, fatty acid, starch, and sucrose metabolism along with fatty acid elongation in mitochondria, glycerolipid, glyoxylate, and dicarboxylate metabolism in adult patients with chronic anemia compared to healthy individuals, which may serve as potential new therapeutic targets. In this review, we aim to (i) summarize current evidence regarding metabolic disturbances in diseases of age-related hematopoietic dysregulation, being represented by multiple myeloma and myelodysplastic syndromes, and in β-thalassemia, a disease model of accelerating cellular aging; and (ii) describe novel therapeutic metabolic-targeted options for the aforementioned diseases, focusing on the need for continuous research in this field.