Biomedical Engineering Reference
In-Depth Information
quiescence and determination of their fate (self-renewal or dif erentiation). In
addition, adhesion molecules also participate in the processes of migration and
homing of hematopoietic stem cells.
Leukemic stem cells share several characteristics with normal hematopoietic
stem cells, including the need for interactions with the microenvironment. For
example, the cross-talk between CXCR4 on leukemic cells and SDF-1 at the niche
is necessary for homing and
in vivo
growth. Moreover, VLA-4 integrins, along with
CXCR4 chemokine receptors, are essential for protection of acute myelogenous
leukemia cells from spontaneous or drug-induced apoptosis. More dif erentiated
leukemic cells, mainly those of acute promyelocytic leukemia, express high levels
of the β1 integrins VLA-4 and VLA-5, express sLe
x
, the ligand of the endothelial
E-selectin and may adhere to the endothelium and extravasate from circulation to
the tissue. One of the most feared complications of acute promyelocytic leukemia
treatment with the all-
trans
retinoic acid (ATRA) and/or arsenic trioxide is
dif erentiation syndrome, characterized by extravascular migration of myeloid
cells and clinically associated with fever, weight gain, dyspnea, pleural ef usion, and
pulmonary ini ltrates on chest radiograph. Dif erent authors had demonstrated
that the treatment with ATRA modulates the expression of adhesive molecules in
acute promyelocytic leukemia cells such as CD11b, CD 18, CDw65, VLA-4, LFA-1,
ICAM-1 (CD54) and Mac-1. Moreover, in contrast with wild-type controls, CD54
or CD18 knockout mice did not present the characteristic increase of myeloid cells
in lung vasculature when injected with acute promyelocytic leukemia cells and
treated with ATRA.
Finally, the expression of adhesion molecules has been associated with
treatment outcome in acute leukemias. CD56 expression was signii cantly
associated with a reduced probability of achieving complete remission as well as
with a shorter survival in acute myelogenous leukemia and with higher frequency
of extramedullary disease in acute lymphoblastic leukemia.
h e accumulating evidence of the role of adhesion molecules in normal and
leukemic hematopoiesis suggests that they are important biomarkers and may be
explored for therapeutic purposes.
INTRODUCTION
h e role of adhesion molecules in migration and activation of mature cells from
peripheral blood has been extensively studied. Nevertheless, only recently is there
accumulating evidence that they play a key role in the physiological control of the
fate, migration and homing of hematopoietic stem cells. In addition, compared
to their normal counterparts, leukemic stem cells and progenitors have a distinct
expression proi le of adhesion molecules, which mediate the interaction with the
bone marrow microenvironment, thus contributing to survival advantage. In
the distinct Acute Myelogenous Leukemia subtype termed Acute Promyelocytic
