Oncogenic role of Pax5 in the T-lymphoid lineage upon ectopic expression from the immunoglobulin heavy-chain locus.

Content Provider	Semantic Scholar
Author	Souabni, Abdallah Jochum, Wolfram Busslinger, Meinrad
Copyright Year	2007
Abstract	Four of 9 PAX transcription factor genes have been associated with chromosomal translocations in human tumors, although their oncogenic potential has not yet been demonstrated in transgenic mouse models. The B-lymphoidPAX5 gene participates in the generation of the t(9;14)(p13;q32) translocation in germinal center B cells, which leads to deregulated PAX5 expression under the control of the immunoglobulin heavy-chain (IgH) locus in a subset of B-cell non-Hodgkin lymphomas. Here we reconstructed a human t(9;14) translocation in a knock-in mouse by inserting a PAX5 minigene into the IgH locus. The IgH(P5ki) allele, which corresponds to a germline rather than somatic mutation, is activated in multipotent hematopoietic progenitors and is subsequently expressed in dendritic cells (DCs) and in natural killer (NK), T, and B cells. Ectopic Pax5 expression interferes with normal T-cell development and causes immature T-lymphoblastic lymphomas in IgH(P5ki/+) and IgH(P5ki/P5ki) mice. Aggressive T-cell lymphomas develop even faster in Ik(Pax5/+) mice expressing Pax5 from the Ikaros locus. Pax5 expression in thymocytes activates B-cell-specific genes and represses T-lymphoid genes, suggesting that Pax5 contributes to lymphomagenesis by deregulating the T-cell gene-expression program. These data identify Pax5 as a potent oncogene and demonstrate that the T-lymphoid lineage is particularly sensitive to the oncogenic action of Pax5.
File Format	PDF HTM / HTML
Alternate Webpage(s)	http://www.bloodjournal.org/content/bloodjournal/109/1/281.full.pdf?sso-checked=true
PubMed reference number	16968900v1
Volume Number	109
Issue Number	1
Journal	Blood
Language	English
Access Restriction	Open
Subject Keyword	B-Lymphocytes Cell development Chromosomal translocation Dendritic Cells Deregulation Diploid Cell Ectopic Gene Expression Leukemogenesis Lymphoma, Non-Hodgkin Natural killer Neoplasms Oncogenes PXN wt Allele Precursor Cell Lymphoblastic Leukemia Lymphoma Precursor cell lymphoblastic lymphoma Somatic mutation Structure of germinal center of lymph node T-Cell Development T-Cell Lymphoma T-Lymphocyte TRANSCRIPTION FACTOR lymphoblast thymocyte
Content Type	Text
Resource Type	Article