@article{8bc22c3d84084011aa8ea6856f024063,
title = "Accelerated progression of chronic lymphocytic leukemia in Em-TCL1 mice expressing catalytically inactive RAG1",
abstract = "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.",
author = "Nganga, {Vincent K.} and Palmer, {Victoria L.} and Hina Naushad and Kassmeier, {Michele D.} and Anderson, {Dirk K.} and Perry, {Greg A.} and Schabla, {Nathan M.} and Swanson, {Patrick C.}",
note = "Funding Information: The National Center for Research Resources of the National Institutes of Health (NIH) provided support for research laboratory construction (C06 RR17417-01) and the Creighton University Funding Information: The authors thank the University of Nebraska Medical Center Microarray Core Facility staff for microarray hybridization services, and Dr Steven Lundy for manuscript review. Support from the Health Future Foundation, the Nebraska LB506 and LB595 Cancer and Smoking Disease Research Programs, and the Nebraska LB692 Biomedical Research Program is gratefully acknowledged. Funding Information: The authors thank the University of Nebraska Medical Center Microarray Core Facility staff for microarray hybridization services, and Dr Steven Lundy for manuscript review. Support from the Health Future Foundation, the Nebraska LB506 and LB595 Cancer and Smoking Disease Research Programs, and the Nebraska LB692 Biomedical Research Program is gratefully acknowledged. The National Center for Research Resources of the National Institutes of Health (NIH) provided support for research laboratory construction (C06 RR17417-01) and the Creighton University Animal Resource Facility (G20RR024001). The University of Nebraska Medical Center Microarray Core Facility receives support from the NCRR (5P20RR016469, RR018788-08) and the National Institute of General Medical Sciences of the NIH (8P20GM103427, GM103471-09). This publication?s contents are the sole responsibility of the authors and do not necessarily represent the official views of the NIH or National Institute of General Medical Sciences",
year = "2013",
month = may,
day = "9",
doi = "10.1182/blood-2012-08-446732",
language = "English (US)",
volume = "121",
pages = "3855--3866",
journal = "Blood",
issn = "0006-4971",
publisher = "American Society of Hematology",
number = "19",
}