Relações entre a patogênese, mecanismos moleculares e tratamento da anemia sideroblástica: uma abordagem multifatorial

Abstract

Anemias correspond to a heterogeneous group of diseases resulting from ineffective erythropoiesis, in which the production of erythrocytes and hemoglobin is impaired, compromising oxygen transport through the bloodstream. This clinical condition can originate from various mechanisms, whether hereditary or acquired. The objective of this work is to contribute to the knowledge of sideroblastic anemia in a multifactorial approach, discussing contexts related to genetics, therapeutic interventions, diagnosis, and subtypes, correlating it with the heme group and iron regulation. For its realization, a literature review of an exploratory-explanatory and qualitative nature was carried out, based on a bibliographic survey using the Medline/Pubmed database, with the terms sideroblastic [Title] OR "Congenital anemia" [Title] and the filter "Free full text". Eighteen articles were eligible after screening and inclusion criteria. This review aims to bring a greater understanding of the subject and also to cooperate with the existing literature, given the lack of studies on the subject. Sideroblastic anemia is a rare condition with unknown epidemiology and diverse causes, which have in common the accumulation of iron in the mitochondria of erythroid precursors in the bone marrow. Iron overload occurs, among other factors, due to the failure in the synthesis of heme, a process that occurs mainly in erythroblasts, through eight enzymatic reactions that are divided between the mitochondria and cytosol of cells. Genetic mutations that culminate in partial loss of function in the enzyme Aminolevulinic Acid Synthase 2 (ALAS2), which has pyridoxine (vitamin B6) as a cofactor, or in the transporter SLC25A38 are the most common causes of congenital sideroblastic anemia, however, interferences in other targets can also lead to this type of anemia. The striking laboratory characteristic observed in patients are ring sideroblasts in Prussian blue staining of bone marrow smears, resulting from the accumulation of iron in the perinuclear mitochondria of erythroblasts, and secondly, cytoplasmic iron inclusions in mature erythrocytes, called Pappenheimer bodies. The severity and responsiveness to treatment are variable. Some patients with ALAS2 mutation respond to supplementation with vitamin B6, as it is an enzymatic cofactor, while in other subtypes blood transfusion therapy associated with iron chelators is often necessary to restore hemoglobin levels and reduce toxic levels of iron. Hematopoietic Stem Cell Transplantation has proven to be a curative therapy, however, there are many limitations to its application. Considering this, advancing studies of new molecules as therapeutic interventions is promising, and one of those that have been applied in this review is luspatercept. Given the breadth of causes, rarity, and variable severity, anemias need to be increasingly well understood to facilitate diagnosis and have more efficient treatment.