| First Author | Shen RR | Year | 2006 |
| Journal | Blood | Volume | 108 |
| Issue | 6 | Pages | 1991-8 |
| PubMed ID | 16728701 | Mgi Jnum | J:115070 |
| Mgi Id | MGI:3690609 | Doi | 10.1182/blood-2006-02-001354 |
| Citation | Shen RR, et al. (2006) Dysregulated TCL1 requires the germinal center and genome instability for mature B-cell transformation. Blood 108(6):1991-8 |
| abstractText | Most lymphomas arise by transformation of germinal center (GC) B cells. TCL1, a proto-oncogene first recognized for its role in T-cell transformation, also induces GC B-cell malignancies when dysregulated in pEmu-B29-TCL1 transgenic (TCL1-tg) mice. Clonal B-cell lymphomas develop from polyclonal populations with latencies of 4 months or more, suggesting that secondary genetic events are required for full transformation. The goals of this study were to determine the GC-related effects of TCL1 dysregulation that contribute to tumor initiation and to identify companion genetic alterations in tumors that function in disease progression. We report that compared with wild-type (WT) cells, B cells from TCL1-tg mice activated in a manner resembling a T-dependent GC reaction show enhanced resistance to FAS-mediated apoptosis with CD40 stimulation, independent of a B-cell antigen receptor (BCR) rescue signal. Mitogenic stimulation of TCL1-tg B cells also resulted in increased expression of Aicda. These GC-related enhancements in survival and Aicda expression could underlie B-cell transformation. Supporting this notion, no B-cell lymphomas developed for 20 months when TCL1-tg mice were crossed onto an Oct coactivator from B cell (OCA-B)-deficient background to yield mice incapable of forming GCs. Spectral karyotype analyses showed that GC lymphomas from TCL1-tg mice exhibit recurrent chromosome translocations and trisomy 15, with corresponding MYC overexpression. We conclude that pEmu-B29-TCL1 transgenic B cells primed for transformation must experience the GC environment and, for at least some, develop genome instability to become fully malignant. |
