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Blood, Vol. 96 No. 2 (July 15), 2000:
pp. 398-404
PLENARY PAPER
Detection of differentially expressed genes in lymphomas using
cDNA arrays: identification of clusterin as a new diagnostic marker for
anaplastic large-cell lymphomas
Axel Wellmann,
Catherine Thieblemont,
Stefania Pittaluga,
Akira Sakai,
Elaine S. Jaffe,
Paul Siebert, and
Mark Raffeld
From the Hematopathology Section, Laboratory of Pathology, National
Cancer Institute, National Institutes of Health, Bethesda, MD; and Gene
Cloning & Analysis, Clontech Laboratories, Palo Alto, CA.
This study reports the first use of gene array technology for the
identification of a tumor-specific marker in lymphoid neoplasms. The
differential gene expression of 31 hematopoietic cell lines, representing most major lymphoma subgroups of B- and T-cell origin, was
assessed by hybridizing labeled complementary DNA to Atlas human
expression arrays containing 588 genes. Genes known to be specific for
B, T, or myelomonocytic lineages were appropriately identified in the
arrays, validating the general utility of this approach. One gene,
clusterin, not previously known to be expressed in lymphoid
neoplasms, was specifically found in all 4 anaplastic large-cell
lymphoma (ALCL) cell lines, but not in any of the 27 remaining tumor
lines. Using a monoclonal antibody against clusterin, its differential
expression was confirmed by Western blotting and immunohistochemistry.
A total of 198 primary lymphomas (representing most major lymphoma
subtypes), including 36 cases of systemic ALCL, were surveyed for
clusterin expression by immunohistochemistry and Western blotting. All
of the 36 ALCL cases marked for clusterin, with most cases showing
moderate to strong staining in the majority of neoplastic cells.
Clusterin expression was not related to expression of anaplastic
lymphoma kinase-1. With 2 exceptions, none of the remaining 162 non-ALCL cases marked with the clusterin antibody, including Hodgkin
disease and primary cutaneous ALCL. In reactive lymphoid tissues, only
follicular dendritic cells and fibroblastic reticular cells exhibited
staining. Clusterin is a highly conserved glycoprotein implicated in
intercellular and cell matrix interactions, regulation of the
complement system, lipid transport, stress responses, and apoptosis.
Although its function in ALCL is unknown, the unique expression of
clusterin within this category of lymphoma provides an additional
marker for the diagnosis of ALCL. This study illustrates the enormous
potential of gene array technologies for diagnostic marker discovery.

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