TCL1 oncogene expression in B cell subsets from lymphoid hyperplasia and distinct classes of B cell lymphoma.
Activation of the TCL1 oncogene has been implicated in T cell leukemias/lymphomas and recently was associated with AIDS diffuse large B cell lymphomas (AIDS-DLBCL). Also, in nonmalignant lymphoid tissues, antibody staining has shown that mantle zone B cells expressed abundant Tcl1 protein, whereas germinal center (GC; centrocytes and centroblasts) B cells showed markedly reduced expression. Here, we analyze isolated B cell subsets from hyperplastic tonsil to determine a more precise pattern of Tcl1 expression with development. We also examine multiple B cell lines and B lymphoma patient samples to determine whether different tumor classes retain or alter the developmental pattern of expression. We show that TCL1 expression is not affected by Epstein-Barr virus (EBV) infection and is high in naïve B cells, reduced in GC B cells, and absent in memory B cells and plasma cells. Human herpesvirus-8 infected primary effusion lymphomas (PEL) and multiple myelomas are uniformly TCL1 negative, whereas all other transformed B cell lines tested express moderate to abundant TCL1. This observation supports the hypothesis that PEL, like myeloma, usually arise from post-GC stages of B cell development. Tcl1 protein is also detected in most naïve/GC-derived B lymphoma patient samples (23 of 27 [85%] positive), whereas most post-GC-derived B lymphomas lack expression (10 of 41 [24%] positive). These data indicate that the pattern of Tcl1 expression is distinct between naïve/GC and post-GC-derived B lymphomas (P < 0.001) and that the developmental pattern of expression is largely retained. However, post-GC-derived AIDS-DLBCL express TCL1 at a frequency equivalent to naïve/GC-derived B lymphomas in immune-competent individuals (7 of 9 [78%] positive), suggesting that TCL1 down-regulation is adversely affected by severe immune system dysfunction. These findings demonstrate that TCL1 expression in B cell lymphoma usually reflects the stage of B cell development from which they derive, except in AIDS-related lymphomas.
Said
J W
JW
Department of Pathology, University of California at Los Angeles School of Medicine, 90095-1732, USA.
Hoyer
K K
KK
French
S W
SW
Rosenfelt
L
L
Garcia-Lloret
M
M
Koh
P J
PJ
Cheng
T C
TC
Sulur
G G
GG
Pinkus
G S
GS
Kuehl
W M
WM
Rawlings
D J
DJ
Wall
R
R
Teitell
M A
MA
D016175:B-Lymphocyte Subsets / Q000378:metabolism*; D002461:Cell Line, Transformed; D002472:Cell Transformation, Viral; D004268:DNA-Binding Proteins / Q000378:metabolism; D015536:Down-Regulation; D018507:Gene Expression Regulation, Developmental; D015972:Gene Expression Regulation, Neoplastic; D004854:Herpesvirus 4, Human / Q000472:pathogenicity; D006801:Humans; D006965:Hyperplasia / Q000235:genetics / Q000378:metabolism; D016483:Lymphoma, AIDS-Related / Q000235:genetics / Q000378:metabolism; D016393:Lymphoma, B-Cell / Q000145:classification / Q000235:genetics* / Q000378:metabolism; D016403:Lymphoma, Large B-Cell, Diffuse / Q000378:metabolism; D009101:Multiple Myeloma / Q000235:genetics / Q000378:metabolism; D014066:Palatine Tonsil / Q000276:immunology; D011518:Proto-Oncogene Proteins / Q000096:biosynthesis / Q000235:genetics* / Q000378:metabolism; D051560:Proto-Oncogene Proteins c-bcl-6; D012333:RNA, Messenger / Q000096:biosynthesis; D014157:Transcription Factors / Q000378:metabolism; D014407:Tumor Cells, Cultured
D004268:DNA-Binding Proteins; D011518:Proto-Oncogene Proteins; D051560:Proto-Oncogene Proteins c-bcl-6; D012333:RNA, Messenger; C090851:TCL1A protein, human; D014157:Transcription Factors