Gene expression profiling of follicular lymphoma and normal germinal center B cells using cDNA arrays.
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 gamma (IL-2R gamma), and IL-4R alpha. 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.
Husson
Hervé
H
Department of Medicine, Harvard Medical School, Boston, MA, USA.
Carideo
Elizabeth G
EG
Neuberg
Donna
D
Schultze
Joachim
J
Munoz
Olivier
O
Marks
Peter W
PW
Donovan
John W
JW
Chillemi
Antoinette C
AC
O'Connell
Peter
P
Freedman
Arnold S
AS
D001402:B-Lymphocytes / Q000737:chemistry*; D002450:Cell Communication / Q000235:genetics; D002453:Cell Cycle / Q000235:genetics; D019941:Cyclin-Dependent Kinase Inhibitor p16 / Q000235:genetics; D050759:Cyclin-Dependent Kinase Inhibitor p21; D018844:Cyclin-Dependent Kinases / Q000235:genetics; D016213:Cyclins / Q000235:genetics; D018076:DNA, Complementary / Q000235:genetics; D004268:DNA-Binding Proteins / Q000235:genetics; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008224:Lymphoma, Follicular / Q000235:genetics*; D009687:Nuclear Proteins / Q000235:genetics; D020411:Oligonucleotide Array Sequence Analysis; D051757:PAX5 Transcription Factor; D012333:RNA, Messenger / Q000032:analysis; D019718:Receptors, CXCR4 / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014157:Transcription Factors / Q000235:genetics; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics; D012359:tRNA Methyltransferases
C493956:CDKN1A protein, human; D019941:Cyclin-Dependent Kinase Inhibitor p16; D050759:Cyclin-Dependent Kinase Inhibitor p21; D016213:Cyclins; D018076:DNA, Complementary; D004268:DNA-Binding Proteins; D009687:Nuclear Proteins; D051757:PAX5 Transcription Factor; C497281:PAX5 protein, human; D012333:RNA, Messenger; D019718:Receptors, CXCR4; D014157:Transcription Factors; D014409:Tumor Necrosis Factor-alpha; C065028:NOP2 protein, human; D012359:tRNA Methyltransferases; D018844:Cyclin-Dependent Kinases