| First Author | Souabni A | Year | 2007 |
| Journal | Blood | Volume | 109 |
| Issue | 1 | Pages | 281-9 |
| PubMed ID | 16968900 | Mgi Jnum | J:118111 |
| Mgi Id | MGI:3698620 | Doi | 10.1182/blood-2006-03-009670 |
| Citation | Souabni A, et al. (2007) Oncogenic role of Pax5 in the T-lymphoid lineage upon ectopic expression from the immunoglobulin heavy-chain locus. Blood 109(1):281-9 |
| abstractText | 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. |
