Erythropoiesis: insights into pathophysiology and treatments in 2017

Abstract

Erythropoiesis is a tightly-regulated and complex process originating in the bone marrow from a multipotent stem cell and terminating in a mature, enucleated erythrocyte.Altered red cell production can result from the direct impairment of medullary erythropoiesis, as seen in the thalassemia syndromes, inherited bone marrow failure as well as in the anemia of chronic disease. Alternatively, in disorders such as sickle cell disease (SCD) as well as enzymopathies and membrane defects, medullary erythropoiesis is not, or only minimally, directly impaired. Despite these differences in pathophysiology, therapies have traditionally been non-specific, limited to symptomatic control of anemia via packed red blood cell (pRBC) transfusion, resulting in iron overload and the eventual need for iron chelation or splenectomy to reduce defective red cell destruction. Likewise, in polycythemia vera overproduction of red cells has historically been dealt with by non-specific myelosuppression or phlebotomy. With a deeper understanding of the molecular mechanisms underlying disease pathophysiology, new therapeutic targets have been identified including induction of fetal hemoglobin, interference with aberrant signaling pathways and gene therapy for definitive cure. This review, utilizing some representative disorders of erythropoiesis, will highlight novel therapeutic modalities currently in development for treatment of red cell disorders.

Evaluation of Erythroferrone, Hepcidin, and Iron Overload Status in Iraqi Transfusion-dependent β-Thalassemia Major Patients

“…They found that ERFE suppresses HEPC via inhibition of hepatic BMP/SMAD signalling by impairing the evolutionary closely related BMP subgroup of BMP5, BMP6, and BMP7 29 . Some studies suggested HEPC therapy and ERFE suppression to the prevention and treatment of iron overload in disorders including β-TM [30][31][32] .…”

Updated Worldwide Epidemiology of Inherited Erythrocyte Disorders

“…The inherited red blood cell (RBC) disorders are typically classified into those affecting hemoglobin synthesis (i.e., hemoglobinopathies), erythrocyte enzymes (enzymopathies), or those resulting from erythrocyte membrane defects [1, 2]. As regards hemoglobinopathies, these are typically caused by mutations and/or deletions in hemoglobin genes, are essentially divided into thalassemias and structural hemoglobin variants, and may cause variable symptoms from mild hypochromic anemia up to severe forms of lifelong and transfusion-dependent anemia [3, 4].…”

“…Disease management in modern healthcare systems, increasingly plagued by limited public funding and reduced economic resources, always requires to garner reliable epidemiologic information that can then be used for implementing healthcare policies aimed at more efficiently preventing, diagnosing and more accurately managing human diseases [7]. Inherited RBC disorders make no exception to this rule, since a timely diagnosis and an effective treatment may be effective to consistently reduce the clinical, societal and economic burden of these conditions [1, 8].…”

Vaccination accelerates hepatic erythroblastosis induced by blood-stage malaria

“…Erythropoiesis is a highly complex process proceeding from the commitment of a haematopoietic stem cell to the megakaryocyte-erythroid lineage, which generates the primitive progenitors of the erythrocyte lineage, i.e., the slowly proliferating burst-forming unit-erythroid cells followed by the rapidly expanding colony-forming unit-erythroid (CFU-e) cells. These in turn are the precursors for the nucleated pro-erythroblasts and erythroblasts [17][18][19], which are arranged in erythroblastic islands organized around a central macrophage [20,21]. Erythroblasts denucleate to reticulocytes which terminally differentiate to erythrocytes [20,22].…”