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Anemia: progress in molecular mechanisms and therapies

Abstract

Anemia is a major source of morbidity and mortality worldwide. Here we review recent insights into how red blood cells (RBCs) are produced, the pathogenic mechanisms underlying various forms of anemia, and novel therapies derived from these findings. It is likely that these new insights, mainly arising from basic scientific studies, will contribute immensely to both the understanding of frequently debilitating forms of anemia and the ability to treat affected patients. Major worldwide diseases that are likely to benefit from new advances include the hemoglobinopathies (β-thalassemia and sickle cell disease); rare genetic disorders of RBC production; and anemias associated with chronic kidney disease, inflammation, and cancer. Promising new approaches to treatment include drugs that target recently defined pathways in RBC production, iron metabolism, and fetal globin-family gene expression, as well as gene therapies that use improved viral vectors and newly developed genome editing technologies.

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Figure 1: A model for hematopoiesis.

Debbie Maizels/Nature Publishing Group

Figure 2: Stimulatory and inhibitory pathways regulating erythropoiesis.

Debbie Maizels/Nature Publishing Group

Figure 3: Regulation of HbF production.

Debbie Maizels/Nature Publishing Group

Figure 4: Regulation of iron homeostasis.

Debbie Maizels/Nature Publishing Group

Figure 5: Gene therapy or editing to treat congenital forms of anemia.

Debbie Maizels/Nature Publishing Group

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Acknowledgements

We apologize for being unable to cite numerous papers and studies in this field due to space limitations. We are grateful to N. Mohandas, A. Nienhuis, and D. Nathan for comments and suggestions on this Review. V.G.S. received support from the US National Institutes of Health (NIH; R01 DK103794, R21 HL120791, U01 HL117720), a March of Dimes Basil O'Connor Scholar Award and an award from the Diamond–Blackfan Anemia Foundation. M.J.W. received support from the NIH (R01 DK0923128, R01 DK61692, R01 HL088554). We are grateful to the many patients with anemia and their families, who have advanced the field by participating in clinical studies and advocating research.

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Correspondence to Vijay G Sankaran or Mitchell J Weiss.

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M.J.W. is a consultant for GlaxoSmithKline and receives research funding for studies on erythropoiesis from Biogen Idec.

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Sankaran, V., Weiss, M. Anemia: progress in molecular mechanisms and therapies. Nat Med 21, 221–230 (2015). https://doi.org/10.1038/nm.3814

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