| First Author | Nganga VK | Year | 2013 |
| Journal | Blood | Volume | 121 |
| Issue | 19 | Pages | 3855-66, S1-16 |
| PubMed ID | 23502221 | Mgi Jnum | J:197927 |
| Mgi Id | MGI:5494906 | Doi | 10.1182/blood-2012-08-446732 |
| Citation | Nganga VK, et al. (2013) Accelerated progression of chronic lymphocytic leukemia in Emu-TCL1 mice expressing catalytically inactive RAG1. Blood 121(19):3855-66, S1-16 |
| abstractText | Chronic lymphocytic leukemia (CLL) is a prevalent B-cell neoplasia that is often preceded by a more benign monoclonal CD5(+) B-cell lymphocytosis. We previously generated transgenic mice expressing catalytically inactive RAG1 (dominant-negative recombination activating gene 1 [dnRAG1] mice) that develop an early-onset indolent CD5(+) B-cell lymphocytosis attributed to a defect in secondary V(D)J rearrangements initiated to edit autoreactive B-cell receptor (BCR) specificity. Hypothesizing that CD5(+) B cells in these animals represent potential CLL precursors, we crossed dnRAG1 mice with CLL-prone Emu-TCL1 mice to determine whether dnRAG1 expression in Emu-TCL1 mice accelerates CLL onset. Consistent with this hypothesis, CD5(+) B-cell expansion and CLL progression occurred more rapidly in double-transgenic mice compared with Emu-TCL1 mice. Nevertheless, CD5(+) B cells in the 2 mouse strains exhibited close similarities in phenotype, immunoglobulin gene usage, and mutation status, and expression of genes associated with immune tolerance and BCR signaling. Gene expression profiling further revealed a potential role for prolactin signaling in regulating BCR editing. These results suggest a model in which benign accumulation of CD5(+) B cells can be initiated through a failure to successfully edit autoreactive BCR specificity and may, in turn, progress to CLL upon introduction of additional genetic mutations. |
