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Blood, 15 April 2002, Vol. 99, No. 8, pp. 2977-2984
NEOPLASIA
The chemokine receptor CCR7 and  4 integrin are important for
migration of chronic lymphocytic leukemia cells into lymph
nodes
Kathleen J. Till,
Ke Lin,
Mirko Zuzel, and
John C. Cawley
From the Department of Haematology, University of
Liverpool, Liverpool, United Kingdom.
Malignant lymphocyte migration into lymph nodes is an important
aspect of chronic lymphocytic leukemia (CLL), yet little is known about
the processes involved. Here we demonstrate that CLL cells migrate
across vascular endothelium in response to at least 3 chemokines,
namely, CCL21, CCL19, and CXCL12. Moreover, transendothelial cell
migration (TEM) in response to CCL21 and CCL19 was significantly higher
for the malignant B cells of patients who had clinical lymph node
involvement as compared with those of patients lacking such
organomegaly. Furthermore, the expression of CCR7, the receptor for
both CCL21 and CCL19, correlated with clinical lymphadenopathy, and
blocking of CCR7 inhibited CLL cell TEM. By using immunohistochemistry we demonstrated that CCL21 and CCL19, but not CXCL12, are located in
high endothelial venules and are, therefore, in an appropriate location
to induce TEM. Regarding the adhesion receptors involved in TEM,  4
(most likely in association with  1) and L2 were shown to be
important in CLL cell TEM in vitro, but only the level of
4 expression correlated with the presence of clinical
lymphadenopathy. The present studies are the first to shed light on the
factors determining CLL cell entry into nodes and define the phenotype of circulating malignant cells likely to determine the pattern of lymph
node enlargement in the disease.
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