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BFU: burst-forming units

CFU: colony-forming units

CFU-E: CFU erythrocyte

CFU-GM: CFU granulocyte and macrophage

CFU-Meg: CFU megakaryocyte

CH3H4PteGlu1: methyltetrahydrofolate

CKD: chronic kidney disease

CoA: coenzyme A

CSF: colony-stimulating factor

dTMP: deoxythymidine monophosphate

dUMP: deoxyuridine monophosphate

ESA: erythropoiesis-stimulating agent

FIGLU: formiminoglutamic acid

G-CSF: granulocyte colony-stimulating factor

GI: gastrointestinal

GM-CSF: granulocyte-macrophage colony-stimulating factor

HFE: high Fe, hereditary hemochromatosis protein, hemeostatic iron regulator

HIF: hypoxia-inducible factor

HIV: human immunodeficiency virus

IL: interleukin

IRE: iron-regulating element

IRP: iron-regulating protein

ITP: immune thrombocytopenia

M-CSF: monocyte-/macrophage-stimulating factor

MDS: myelodysplastic syndromes

PBSC: peripheral blood stem cell

PteGlu: pteroylglutamic acid, folic acid

rHuMGDF: recombinant human megakaryocyte growth and development factor

SAM: S-adenosylmethionine

TPO: thrombopoietin

TRA: thrombopoietin receptor agonist

TGFβ: transforming growth factor β

VHL: von Hippel-Lindau


The finite life span of most mature blood cells requires their continuous replacement, a process termed hematopoiesis. New cell production must respond to basal needs and states of increased demand. Erythrocyte production can increase more than 20-fold in response to anemia or hypoxemia, leukocyte production increases dramatically in response to systemic infections, and platelet production can increase 10- to 20-fold when platelet consumption results in thrombocytopenia.

The regulation of blood cell production is complex. Hematopoietic stem cells are rare marrow cells that manifest self-renewal and lineage commitment, resulting in cells destined to differentiate into the 10 or more distinct blood cell lineages. For the most part, this process occurs in the marrow cavities of the skull, vertebral bodies, pelvis, and proximal long bones; it involves interactions among hematopoietic stem and progenitor cells and the cells and complex macromolecules of the marrow stroma and is influenced by a number of soluble and membrane-bound hematopoietic growth factors. Several hormones and cytokines have been identified and cloned that affect hematopoiesis, permitting their production in quantities sufficient for research and, in some cases, therapeutic use. Clinical applications range from the treatment of primary hematological diseases (e.g., aplastic anemia, congenital neutropenia) to use as adjuncts in the treatment of severe infections and in the management of patients with kidney failure or those undergoing cancer chemotherapy or marrow transplantation.

Hematopoiesis also requires an adequate supply of minerals (e.g., iron, cobalt, and copper) and vitamins (e.g., folic acid, vitamin B12, pyridoxine, ascorbic acid, and riboflavin); deficiencies generally result in characteristic anemias or, less frequently, a general failure of hematopoiesis (Rojas-Hernandez and Oo, 2018). Therapeutic correction of a specific deficiency state depends on the accurate diagnosis of the basis for the anemia and on knowledge about the correct dose, formulation, and route of administration of the deficient mineral(s) or vitamin(s).


Steady-state hematopoiesis encompasses the tightly regulated production of more than 400 billion blood cells each day. The hematopoietic organ also is unique in adult physiology in that several mature cell types are ...

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