Biomedical Engineering Reference
In-Depth Information
migration. Conversely, excess of CD38 resulted in arrest of the blasts within the
bone marrow through hyaluronate adhesion (Gallay
et al
. 2007).
Besides acute myelogenous leukemia, adhesive defects have also been described
in acute lymphoblastic leukemia. Bradstock
et al
. (2000) have demonstrated that
acute lymphoblastic leukemia blasts migrate into layers of bone marrow i broblasts
in vitro
by using the α1 integrins VLA-4 and VLA-5. Accordingly, Kollet
et al
.
(2001) have shown that homing of leukemic acute lymphoblastic leukemia blasts
into the bone marrow of NOD/SCID mice is dependent on VLA-4, VLA-5, and
LFA-1.
ADHESION MOLECULES AND ACUTE PROMYELOCYTIC
LEUKEMIA
Several acute leukemia subtypes are known to express adhesion molecules.
However, acute promyelocytic leukemia represents the paradigm of the clinical
importance of these molecules. It is characterized by a balanced reciprocal
translocation between chromosomes 15 and 17. As a result, the
Promyelocytic
Leukemia
(PML) gene is translocated and fused with the
Retinoic Acid Receptor α
(RARα) generating the PML/RARα hybrid gene. h e PML/RARα fusion protein
acts as a transcription repressor blocking the dif erentiation of acute promyelocytic
leukemia blasts at the stage of promyelocytes. In immunophenotypic terms, acute
promyelocytic leukemia cells express myeloid markers such as CD33 and CD117,
while the expression of CD13 is variable. In addition, mature myeloid antigens,
such as CD15 and CD14, are expressed weakly or are absent. Furthermore, there
appears to be an increased incidence of expression of the neural cell adhesion
molecule (NCAM), CD56, which has been associated with poor clinical outcome
in acute promyelocytic leukemia. Acute promyelocytic leukemia cells present some
dif erences in the expression of adhesive molecules when compared to neutrophils:
they express high levels of the β1 integrins VLA-4 and VLA-5 and lower levels of
CD11b and usually express sLe
x
, the ligand of E-selectin that probably contributes
to adherence to E-selectin on activated endothelium (Di Noto
et al.
1994).
Currently, the use of ATRA- and anthracycline-based chemotherapy represents
the mainstay in treatment of acute promyelocytic leukemia, inducing complete
hematological and molecular remission in a high proportion of patients. ATRA
induces the malignant cells to dif erentiate into phenotypically mature myeloid cells,
and this dif erentiation determines the activation of several leukocyte functions
including expression of adhesion molecules and secretion of cytokines (Di Noto
et al
.
1994). Acute promyelocytic leukemia cells attach to a layer of endothelial
cells in a manner similar to neutrophils. Moreover, acute promyelocytic leukemia
cells produce IL-1, which might sustain their growth and induce local activation
of adhesion molecules on the endothelium, leading to an increase of adhesiveness
of the blasts.
