Biomedical Engineering Reference
In-Depth Information
Fig. 1
Homing and mobilization in the hematopoietic stem cells niches. Hematopoietic stem
cells express a number of adhesion molecules on their surface that are important to both homing
and mobilization. Key molecules involved in these processes are selectins, integrins, CD44 and
their ligands. Chemokines are important in guiding the homing of stem cells from the periphery
into the bone marrow and ultimately into the stem cell niche.
Color image of this i gure appears in the color plate section at the end of the topic.
stem cells, HCELL is the most potent E- and L-selectin ligand, mediating these
binding hemodynamic l ow conditions.
Leukemic stem cells, also named leukemia-initiating cells, are derived from
hematopoietic stem cells or proliferating progenitor cells through the acquisition
of stem cell properties. In acute myelogenous leukemia, it has been demonstrated
that interaction between CXCR4 on leukemic cells and SDF-1 at the niche is
necessary for proper homing and
in vivo
growth of leukemic cells, suggesting
that leukemic stem cells as the normal hematopoietic stem cells may require
niche interactions (Tavor
et al
. 2004). Moreover, it has been demonstrated that
the VLA-4 integrins, along with CXCR4 chemokine receptors, are essential for
protection of acute myelogenous leukemia cells from spontaneous or drug-
induced apoptosis (Delforge
et al
. 2005, Spoo
et al
. 2007). VLA-4-expressing
acute myelogenous leukemia cells can better adhere to i bronectin and stromal
cells in response to cytokine stimulation, thereby protecting them from apoptosis
in vitro
and possibly leading to minimal residual disease
in vivo
with the potential
to trigger leukemic relapse (Matsunaga
et al
. 2003). Other relevant adhesion
molecules expressed by acute myelogenous leukemia blasts are PECAM (CD31)
and CD38 that mediate the interaction with microenvironmental elements, i.e.,
CD31 on the surface of marrow endothelial cells (CD31/CD31 and CD38/CD31
interactions) and hyaluronate (CD38/hyaluronate interactions). Excess of CD31
relative to CD38 on the cell membrane of leukemic cells promoted a homotypic
interaction with marrow endothelial cells, resulting in higher transendothelial
