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Blood, 1 January 2002, Vol. 99, No. 1, pp. 282-289
NEOPLASIA
Gene expression profiling of follicular lymphoma and normal
germinal center B cells using cDNA arrays
Hervé Husson,
Elizabeth G. Carideo,
Donna Neuberg,
Joachim Schultze,
Olivier Munoz,
Peter W. Marks,
John W. Donovan,
Antoinette C. Chillemi,
Peter O'Connell, and
Arnold S. Freedman
From the Department of Medicine, Harvard Medical
School, and the Department of Adult Oncology and Department of
Biostatistical Science, Dana-Farber Cancer Institute, Boston, MA; and
the Breast Center, Baylor College of Medicine, Houston, TX.
Follicular lymphomas (FLs) are neoplastic counterparts of normal
germinal center (GC) B cells. FLs are characterized by t(14;18) with
deregulation of the Bcl-2 (BCL2) gene. The
presence of t(14;18) and overexpression of Bcl-2 is
necessary, but not sufficient, to cause this disease. An array
containing 588 complementary DNAs (cDNAs) was used to compare the gene
expression between GC B cells and FL cells. To specifically monitor
genes expressed in normal GC B and FL cells and not the entire tissue
compartment, normal and malignant B cells were purified from tissues.
Using the array, 37 genes were up-regulated and 28 were down-regulated
in FL cells as compared to normal GC B cells. The expression level of
each differentially expressed gene was verified by quantitative
polymerase chain reaction. Following these studies 24 genes were
up-regulated and 8 genes down-regulated with a P value less
than .1. Included among the genes that were up-regulated in FLs were
cell cycle regulator proteins CDK10, p120, p21CIP1, and p16INK4A;
transcription factors/regulators Pax-5 and Id-2, which are involved in
normal B-cell development; and genes involved in cell-cell
interactions, tumor necrosis factor, interleukin-2R (IL-2R), and
IL-4R . Among the genes that were down-regulated in FLs were
MRP8 and MRP14, which are involved in adhesion.
Interestingly, several of these genes are localized within chromosomal
regions already described to be altered in FLs. These findings provide
a basis for future studies into the pathogenesis and pathophysiology of
FL and may lead to the identification of potential therapeutic targets
as well as antigens for immunotherapeutic strategies.
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