Titre du document / Document title

Endothelial cell activation by myeloblasts: molecular mechanisms of leukostasis and leukemic cell dissemination

Auteur(s) / Author(s)

STUCKI Anne ⁽¹⁾ ; RIVIER Anne-Sophie ⁽¹⁾ ; GIKIC Milica ⁽¹⁾ ; MONAI Natacha ⁽¹⁾ ; SCHAPIRA Marc ⁽¹⁾ ; SPERTINI Olivier ⁽¹⁾ ;

Affiliation(s) du ou des auteurs / Author(s) Affiliation(s)

⁽¹⁾ Division and Central Laboratory of Hematology, Centre Hospitalier Universitaire Vaudois, Lausanne, SUISSE

Résumé / Abstract

Leukostasis and tissue infiltration by leukemic cells are poorly understood life-threatening complications of acute leukemia. This study has tested the hypothesis that adhesion receptors and cytokines secreted by blast cells play central roles in these reactions. Immunophenotypic studies showed that acute myeloid leukemia (AML) cells (n = 78) of the MO to M5 subtypes of the French-American-British Cooperative Group expressed various amounts of adhesion receptors, including CD11a, b, c/CD18, CD49d, e, f/CD29, CD54, sCD15, and L-selectin. The presence of functional adhesion receptors was evaluated using a nonstatic adhesion assay. The number of blast cells attached to unactivated endothelium increased by 7 to 31 times after a 6-hour exposure of endothelium to tumor necrosis factor (TNF)-α. Inhibition studies showed that multiple adhesion receptors-including L-selectin, E-selectin, VCAM-1, and CD11/CD18-were involved in blast cell adhesion to TNF-α-activated endothelium. Leukemic cells were then cocul-tured at 37°C on unactivated endothelial cell monolayers for time periods up to 24 hours. A time-dependent increase in the number of blasts attached to the endothelium and a concomitant induction of ICAM-1, VCAM-1, and E-selectin were observed. Additional experiments revealed that endothelial cell activation by leukemic myeloblasts was caused by cytokine secretion by blast cells, in particular TNF-α and IL-1β, and direct contacts between adhesion receptors expressed by blast cells and endothelial cells. Thus, leukemic cells have the ability to generate conditions that promote their own adhesion to vascular endothelium, a property that may have important implications for the pathophysiology of leukostasis and tissue infiltration by leukemic blast cells.

Revue / Journal Title

Blood   ISSN 0006-4971 

Source / Source

2001, vol. 97, n^o7, pp. 2121-2129 (82 ref.)

Langue / Language

Anglais

Editeur / Publisher

The Americain Society of Hematology, Washington, DC, ETATS-UNIS  (1946) (Revue)

Mots-clés anglais / English Keywords

Acute myelocytic leukemia ; Complication ; Leukocytosis ; Tumor cell ; Endothelial cell ; Vascular wall ; Intercellular adhesion molecule 1 ; E Selectin ; Myeloblast ; Vascular cell adhesion molecule 1 ; Adhesion ; Cell adhesion molecule ; Tumor necrosis factor α ; Interleukin 1β ; Biological receptor ; Pathophysiology ; Human ; Acute ; Leukostasis ; Malignant hemopathy ; Cytokine ;

Mots-clés français / French Keywords

Leucémie myéloblastique ; Complication ; Leucocytose ; Cellule tumorale ; Cellule endothéliale ; Paroi vasculaire ; Protéine ICAM1 ; Sélectine E ; Myéloblaste ; Protéine VCAM1 ; Adhérence ; Protéine CAM ; Facteur nécrose tumorale α ; Interleukine 1β ; Récepteur biologique ; Physiopathologie ; Homme ; Aigu ; Leucostase ; Hémopathie maligne ; Cytokine ;

Mots-clés espagnols / Spanish Keywords

Leucemia mieloblástica ; Complicación ; Leucocitosis ; Célula tumoral ; Célula endotelial ; Pared vascular ; Proteína ICAM1 ; Selectin E ; Mieloblasto ; Proteína VCAM1 ; Adherencia ; Proteína CAM ; Factor necrosis tumoral α ; Interleuquina 1β ; Receptor biológico ; Fisiopatología ; Hombre ; Agudo ; Hemopatía maligna ; Citoquina ;

Localisation / Location

INIST-CNRS, Cote INIST : 3178, 35400009874786.0310