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Regulation of myelopoiesis

Colin A Sieff, MB, BCh, FRCPath
Section Editor
Laurence A Boxer, MD
Deputy Editor
Jennifer S Tirnauer, MD


The production of myeloid cells (granulocytes and monocytes) is a tightly regulated process. During steady state hematopoiesis, approximately 108 to 109 of these cells are produced per hour in the bone marrow to maintain their circulating numbers within fairly narrow limits. Production can be rapidly increased in the setting of infection or inflammation. The terms leukocytes and granulocytes are often used interchangeably, although they are somewhat different. The term leukocyte comprises granulocytes, monocytes, and lymphocytes, while the term granulocyte includes polymorphonuclear neutrophils (PMNs), eosinophils, and basophils.

Myelopoiesis begins with the differentiation of a small pool of multipotent hematopoietic stem cells into the most primitive myeloid progenitors. These progenitors develop into recognizable myeloid precursors, which subsequently follow a specific differentiation program that culminates in the emergence of mature neutrophils, eosinophils, basophils and monocytes (figure 1). This process is most likely driven by expression of successive combinations of transcription factors that in turn dictate the expression of adhesion and hematopoietic growth factor receptors (HGFRs):

Adhesion receptors play an important role in the localization and release of maturing cells from specific niches in the bone marrow.

Hematopoietic growth factors (HGFs), such as stem cell factor (SCF, also called Steel factor or c-kit ligand), interleukin (IL)-3, granulocyte-macrophage colony-stimulating factor (GM-CSF), and granulocyte colony-stimulating factor (G-CSF) are important for the amplification of progenitor cells, and bind to their target cells through specific receptors.

G-CSF is essential for the amplification and terminal differentiation of neutrophil progenitors and precursors, while macrophage colony-stimulating factor (M-CSF, CSF1) and IL-5 are lineage specific factors for the monocyte and eosinophil lineages, respectively.


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