TY - JOUR
T1 - The human BCL6 transgene promotes the development of lymphomas in the mouse
AU - Baron, Beverly W.
AU - Anastasi, John
AU - Montag, Anthony
AU - Huo, Dezheng
AU - Baron, Rebecca M.
AU - Karrison, Theodore
AU - Thirman, Michael J.
AU - Subudhi, Sumit K.
AU - Chin, Robert K.
AU - Felsher, Dean W.
AU - Fu, Yang Xin
AU - McKeithan, Timothy W.
AU - Baron, Joseph M.
PY - 2004/9/28
Y1 - 2004/9/28
N2 - BCL6, a gene on chromosome 3, band q27, encodes a zinc finger transcriptional repressor that is needed for germinal center formation and has been implicated in the pathogenesis of some human lymphomas when it is mutated or involved in chromosomal rearrangements. To explore further the mechanisms of action of BCL6 in lymphomagenesis, we developed a transgenic mouse model mimicking a common translocation, the t(3, 14)(q27;q32), in human lymphomas. The transgenic mice develop normally and express the transgenic BCL6 protein constitutively in lymphocytes. A small fraction of the animals develop B and T cell lymphomas after a long latency period, but the incidence is dramatically enhanced following administration of N-ethyl-N-nitrosourea, a carcinogen that induces DNA mutations. The N-ethyl-N-nitrosourea-induced lymphomas spread widely, were exclusively T cell, expressed the BCL6 protein, and occurred only in the transgenic mice. Because BCL6 expression has been reported in a number of T cell tumors as well as in the more commonly occurring B cell lymphomas in humans, our transgenic mice provide a model for the study of human lymphomas.
AB - BCL6, a gene on chromosome 3, band q27, encodes a zinc finger transcriptional repressor that is needed for germinal center formation and has been implicated in the pathogenesis of some human lymphomas when it is mutated or involved in chromosomal rearrangements. To explore further the mechanisms of action of BCL6 in lymphomagenesis, we developed a transgenic mouse model mimicking a common translocation, the t(3, 14)(q27;q32), in human lymphomas. The transgenic mice develop normally and express the transgenic BCL6 protein constitutively in lymphocytes. A small fraction of the animals develop B and T cell lymphomas after a long latency period, but the incidence is dramatically enhanced following administration of N-ethyl-N-nitrosourea, a carcinogen that induces DNA mutations. The N-ethyl-N-nitrosourea-induced lymphomas spread widely, were exclusively T cell, expressed the BCL6 protein, and occurred only in the transgenic mice. Because BCL6 expression has been reported in a number of T cell tumors as well as in the more commonly occurring B cell lymphomas in humans, our transgenic mice provide a model for the study of human lymphomas.
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U2 - 10.1073/pnas.0406138101
DO - 10.1073/pnas.0406138101
M3 - Article
C2 - 15375218
AN - SCOPUS:4644302712
SN - 0027-8424
VL - 101
SP - 14198
EP - 14203
JO - Proceedings of the National Academy of Sciences of the United States of America
JF - Proceedings of the National Academy of Sciences of the United States of America
IS - 39
ER -