Increased expression of germinal center-associated nuclear protein RNA-primase is associated with lymphomagenesis.
Lymphomas arise containing abnormalities of various differentiation stage-specific molecules. In the study reported here, we have shown abnormal up-regulation of germinal center B cell-associated GANP in various human lymphomas including mantle cell, diffuse large B cell, and Hodgkin lymphoma, by immunohistochemical analysis. To study the role of GANP in lymphomagenesis, we generated mutant mice (ganp-Tg) that express the transgenic ganp gene under immunoglobulin enhancer and promoter control. Ganp-Tg mice showed a high incidence of lymphomagenesis (29.5%) after aging with a non-B/non-T cell surface phenotype having slight CD45R/B220 expression and Ig transcripts of rearranged VH-DH-JH IgH loci. Lymphomas generated in ganp-Tg mice displayed similar pathologic characteristics to mouse reticulum cell neoplasm or Hodgkin lymphoma-like lesions. The VH sequences of individual mice showed that the tumors proliferated from a single clone or oligoclones, as is found in human diffuse large B-cell lymphomas and Hodgkin lymphoma. These results suggest that GANP overexpression is a causative factor in the generation of B lymphomas.
Department of Immunology, Graduate School of Medical Sciences, Kumamoto University, Honjo, Kumamoto, Japan.
Satoru
S
Fujimura
Yan
Y
Xing
Motohiro
M
Takeya
Yasuyuki
Y
Yamashita
Koichi
K
Ohshima
Kazuhiko
K
Kuwahara
Nobuo
N
Sakaguchi
D000123:Acetyltransferases / Q000096:biosynthesis* / Q000235:genetics; D000818:Animals; D002471:Cell Transformation, Neoplastic / Q000235:genetics / Q000378:metabolism*; D019915:DNA Primase / Q000096:biosynthesis* / Q000235:genetics; D005260:Female; D015321:Gene Rearrangement; D005803:Genes, Immunoglobulin; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins; D016393:Lymphoma, B-Cell / Q000201:enzymology / Q000235:genetics / Q000378:metabolism*; D008297:Male; D051379:Mice; D008822:Mice, Transgenic; D010750:Phosphoproteins / Q000096:biosynthesis* / Q000235:genetics; D011401:Promoter Regions, Genetic; D015854:Up-Regulation
D047908:Intracellular Signaling Peptides and Proteins; D010750:Phosphoproteins; D000123:Acetyltransferases; C406825:MCM3AP protein, human; D019915:DNA Primase