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High levels of the shed form of L-selectin are present in patients with
acute leukemia and inhibit blast cell adhesion to activated endothelium
O Spertini, P Callegari, AS Cordey, J Hauert, J Joggi, V von Fliedner and M Schapira
Division of Hematology, University of Lausanne, Switzerland.
L-selectin is expressed by most leukocytes and mediates the initial step of
adhesion to vascular endothelium. A feature of this adhesion receptor is to
be shed from the cell surface. We report here the presence of high levels
of the shed form of L-selectin (sL-selectin) in plasma from patients with
acute leukemia. We also show that sL-selectin purified from acute leukemia
plasma exhibits functional activity. The mean (+/- 1 SD) plasma level of
sL-selectin among 100 healthy individuals was 2.1 +/- 0.7 micrograms/mL.
This value was increased (> 2 SD above the mean) in 63% of 58 patients
with acute lymphoblastic leukemia (ALL) and 59% of 93 patients with acute
myelogenous leukemia ([AML] P < .001). Repeated measurements in 24
patients showed normal- range levels in 16 of 16 patients in complete
remission and high levels in eight of eight patients with therapy-resistant
acute leukemia or leukemia relapse. Furthermore, elevated sL-selectin
levels were detected in cerebrospinal fluid of three patients with ALL
suffering from a relapse limited to the central nervous system. Epitope
mapping with monoclonal antibodies demonstrated that L-selectin shedding
from leukemic blasts was accompanied by conformational changes of its
epidermal growth factor-like domain. A functional role for sL-selectin
purified from leukemic plasma was supported by its ability to completely
inhibit L-selectin-dependent adhesion of blast cells to tumor necrosis
factor-alpha (TNF-alpha)-activated endothelium in vitro. These results
suggest that sL-selectin may have an important role in the regulation of
leukemic cell adhesion to endothelium. In addition, monitoring of the
sL-selectin level may be useful for evaluating leukemia activity, in
particular for the detection of leukemia relapse.
Volume 84,
Issue 4,
pp. 1249-1256,
08/15/1994
Copyright © 1994 by The American Society of Hematology
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