High levels of the shed form of L-selectin are present in patients with acute leukemia and inhibit blast cell adhesion to activated endothelium

• Published in: Blood 1994-08, Vol.84 (4), p.1249-1256
• Main Authors: SPERTINI, O, CALLEGARI, P, CORDEY, A.-S, HAUERT, J, JOGGI, J, VON FLIEDNER, V, SCHAPIRA, M
• Format: Article
• Language: English
• Subjects: Antigens, CD - blood; Antineoplastic Combined Chemotherapy Protocols - therapeutic use; Biological and medical sciences; Biomarkers, Tumor - blood; Blast Crisis - immunology; Blotting, Western; Cell Adhesion; Cell Adhesion Molecules - blood; Cells, Cultured; Endothelium, Vascular - physiology; Enzyme-Linked Immunosorbent Assay; Hematologic and hematopoietic diseases; Humans; Immunophenotyping; L-Selectin; Leukemia, Myeloid, Acute - blood; Leukemia, Myeloid, Acute - drug therapy; Leukemia, Myeloid, Acute - immunology; Leukemia, Myeloid, Acute - pathology; Leukemias. Malignant lymphomas. Malignant reticulosis. Myelofibrosis; Lymphocytes - immunology; Medical sciences; Precursor Cell Lymphoblastic Leukemia-Lymphoma - blood; Precursor Cell Lymphoblastic Leukemia-Lymphoma - drug therapy; Precursor Cell Lymphoblastic Leukemia-Lymphoma - immunology; Precursor Cell Lymphoblastic Leukemia-Lymphoma - pathology; Predictive Value of Tests; Prognosis; Reference Values; Umbilical Veins
• ISSN: 0006-4971; 1528-0020
• DOI: 10.1182/blood.v84.4.1249.1249

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.