Accelerated progression of chronic lymphocytic leukemia in Em-TCL1 mice expressing catalytically inactive RAG1

Vincent K. Nganga, Victoria L. Palmer, Hina Naushad, Michele D. Kassmeier, Dirk K. Anderson, Greg A. Perry, Nathan M. Schabla, Patrick C. Swanson

Research output: Contribution to journalArticlepeer-review

22 Scopus citations


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 Eμ-TCL1 mice to determine whether dnRAG1 expression in Eμ-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 Eμ-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.

Original languageEnglish (US)
Pages (from-to)3855-3866
Number of pages12
Issue number19
StatePublished - May 9 2013

All Science Journal Classification (ASJC) codes

  • Biochemistry
  • Immunology
  • Hematology
  • Cell Biology


Dive into the research topics of 'Accelerated progression of chronic lymphocytic leukemia in Em-TCL1 mice expressing catalytically inactive RAG1'. Together they form a unique fingerprint.

Cite this