pubmed.ncbi.nlm.nih.gov

Erythropoiesis: insights into pathophysiology and treatments in 2017 - PubMed

  • ️Mon Jan 01 2018

Review

Erythropoiesis: insights into pathophysiology and treatments in 2017

Andrea Zivot et al. Mol Med. 2018.

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.

Keywords: Erythropoiesis; Red cell disorders; Therapy.

PubMed Disclaimer

Conflict of interest statement

Ethics approval and consent to participate

Not applicable.

Consent for publication

Not applicable.

Competing interests

The authors declare that they have no competing interests.

Publisher’s Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Figures

Fig. 1
Fig. 1

Overview of erythropoiesis, from the hematopoietic stem cell (HSC) to the red blood cell (RBC). Erythropoiesis takes place in the bone marrow, and erythroblastic islands are niches for erythropoiesis from the CFU-E to the reticulocyte state. Then the reticulocyte reaches the blood stream where it achieves its maturation by losing its internal organelles, remodeling its plasma membrane and finally becomes a RBC

Similar articles

Cited by

References

    1. Acquaye C, Blanchette-Mackie EJ, Reindorf C, Edelstein S, Schechter AN. Electron microscopic studies of the intracellular polymerization of sickle hemoglobin. Blood Cells. 1988;13:359–376. - PubMed
    1. Aguilar-Lopez LB, Delgado-Lamas JL, Rubio-Jurado B, Perea FJ, Ibarra B. Thalidomide therapy in a patient with thalassemia major. Blood Cells Mol Dis. 2008;41:136–137. doi: 10.1016/j.bcmd.2008.03.001. - DOI - PubMed
    1. Aljurf M, et al. Abnormal assembly of membrane proteins in erythroid progenitors of patients with beta-thalassemia major. Blood. 1996;87:2049–2056. - PubMed
    1. An X, Schulz VP, Mohandas N, Gallagher PG. Human and murine erythropoiesis. Curr Opin Hematol. 2015;22:206–211. doi: 10.1097/MOH.0000000000000134. - DOI - PMC - PubMed
    1. Andersen CL, et al. A phase II study of vorinostat (MK-0683) in patients with primary myelofibrosis and post-polycythemia vera myelofibrosis. Haematologica. 2014;99:e5–e7. doi: 10.3324/haematol.2013.096669. - DOI - PMC - PubMed

Publication types

MeSH terms