Page 20 - Essential Haematology

6 / Chapter 1 Haemopoiesis

liver and muscle. The contribution of adult donor Haemopoietic g rowth f actors
haemopoietic cells to non - haemopoietic tissues is at

The haemopoietic growth factors are glycoprotein

most very small. The persistence of pluripotential
hormones that regulate the proliferation and dif-
stem cells in postnatal life, the presence of mesen-
ferentiation of haemopoietic progenitor cells and
chymal stem cells in bone marrow and fusion of
the function of mature blood cells. Th ey may act
transplanted cells with host cells have all been pro-
locally at the site where they are produced by cell –
posed to explain many of the fi ndings suggesting

cell contact or circulate in plasma. They also bind
stem cell ‘ plasticity ’ .
to the extracellular matrix to form niches to which

stem and progenitor cells adhere. The growth factors
The r egulation of h aemopoiesis may cause cell proliferation but can also stimulate

differentiation, maturation, prevent apoptosis and
Haemopoiesis starts with stem cell division in which
affect the function of mature cells (Fig. 1.6 ).

one cell replaces the stem cell ( self - renewal ) and the

They share a number of common properties
other is committed to diff erentiation. Th ese early
(Table 1.2 ) and act at different stages of haemopoi-

committed progenitors express low levels of tran-
esis (Table 1.3 ; Fig. 1.7 ). Stromal cells are the major
scription factors that may commit them to discrete
cell lineages. Which cell lineage is selected for dif-
ferentiation may depend both on chance and on the
external signals received by progenitor cells. Several
Table 1.3 Haemopoietic growth factors.

transcription factors (see p. 13 ) regulate survival of
stem cells (e.g. SCL, GATA - 2, NOTCH - 1) whereas
Act on stromal cells
others are involved in differentiation along the

IL - 1
major cell lineages. For instance, PU.1 and the
TNF
CEBP family commit cells to the myeloid lineage
whereas GATA - 1 and FOG - 1 have an essential Act on pluripotential stem cells
roles in erythropoietic and megakaryocytic SCF
diff erentiation. FLT3 - L
VEGF
Act on multipotential progenitor cells
IL - 3

Table 1.2 General characteristics of myeloid GM - CSF
and lymphoid growth factors.
IL - 6
G - CSF
Glycoproteins that act at very low concentrations
Thrombopoietin
Act hierarchically
Act on committed progenitor cells
Usually produced by many cell types G - CSF *

M - CSF
Usually affect more than one lineage
IL - 5 (eosinophil - CSF)
Usually active on stem/progenitor cells and on Erythropoietin
functional end cells Thrombopoietin *

Usually show synergistic or additive interactions
with other growth factors CSF, colony - stimulating factor; FLT3 - L, FLT3 ligand;
G - CSF, granulocyte colony - stimulating factor; GM - CSF,
Often act on the neoplastic equivalent of a granulocyte – macrophage colony - stimulating factor; IL,
normal cell interleukin; M - CSF, macrophage colony - stimulating factor;
SCF, stem cell factor; TNF, tumour necrosis factor; VEGF,
Multiple actions: proliferation, differentiation, vascular endothelial growth factor.

maturation, functional activation, prevention of * These also act synergistically with early acting factors on
pluripotential progenitors.
apoptosis of progenitor cells