Transgenic mouse model of IgM + lymphoproliferative disease mimicking Waldenström macroglobulinemia.

Autor: Tompkins VS; Department of Pathology, Iowa Institute of Human Genetics, University of Iowa Roy J. and Lucille A. Carver College of Medicine, Iowa City, IA, USA., Sompallae R; Department of Pathology, Iowa Institute of Human Genetics, University of Iowa Roy J. and Lucille A. Carver College of Medicine, Iowa City, IA, USA.; Bioinformatics Division, Iowa Institute of Human Genetics, University of Iowa Roy J. and Lucille A. Carver College of Medicine, Iowa City, IA, USA., Rosean TR; Department of Pathology, Iowa Institute of Human Genetics, University of Iowa Roy J. and Lucille A. Carver College of Medicine, Iowa City, IA, USA., Walsh S; Department of Radiology, University of Iowa Roy J. and Lucille A. Carver College of Medicine, Iowa City, IA, USA., Acevedo M; Department of Radiology, University of Iowa Roy J. and Lucille A. Carver College of Medicine, Iowa City, IA, USA., Kovalchuk AL; Virology and Cellular Immunology Section, Laboratory of Immunogenetics, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Rockville, MD, USA., Han SS; Department of Pathology, Iowa Institute of Human Genetics, University of Iowa Roy J. and Lucille A. Carver College of Medicine, Iowa City, IA, USA., Jing X; Department of Pathology, Iowa Institute of Human Genetics, University of Iowa Roy J. and Lucille A. Carver College of Medicine, Iowa City, IA, USA., Holman C; Department of Pathology, Iowa Institute of Human Genetics, University of Iowa Roy J. and Lucille A. Carver College of Medicine, Iowa City, IA, USA., Rehg JE; Department of Pathology, St Jude Children's Research Hospital, Memphis, TN, USA., Herms S; International Waldenstrom's Macroglobulinemia Foundation, Sarasota, FL, USA., Sunderland JS; Department of Radiology, University of Iowa Roy J. and Lucille A. Carver College of Medicine, Iowa City, IA, USA., Morse HC; Virology and Cellular Immunology Section, Laboratory of Immunogenetics, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Rockville, MD, USA., Janz S; Department of Pathology, Iowa Institute of Human Genetics, University of Iowa Roy J. and Lucille A. Carver College of Medicine, Iowa City, IA, USA.
Jazyk: angličtina
Zdroj: Blood cancer journal [Blood Cancer J] 2016 Nov 04; Vol. 6 (11), pp. e488. Date of Electronic Publication: 2016 Nov 04.
DOI: 10.1038/bcj.2016.95
Abstrakt: Waldenström macroglobulinemia (WM) is a low-grade incurable immunoglobulin M + (IgM + ) lymphoplasmacytic lymphoma for which a genetically engineered mouse model of de novo tumor development is lacking. On the basis of evidence that the pro-inflammatory cytokine, interleukin 6 (IL6), and the survival-enhancing oncoprotein, B cell leukemia 2 (BCL2), have critical roles in the natural history of WM, we hypothesized that the enforced expression of IL6 and BCL2 in mice unable to perform immunoglobulin class switch recombination may result in a lymphoproliferative disease that mimics WM. To evaluate this possibility, we generated compound transgenic BALB/c mice that harbored the human BCL2 and IL6 transgenes, EμSV-BCL2-22 and H2-L d -hIL6, on the genetic background of activation-induced cytidine deaminase (AID) deficiency. We designated these mice BCL2 + IL6 + AID - and found that they developed-with full genetic penetrance (100% incidence) and suitably short latency (93 days median survival)-a severe IgM + lymphoproliferative disorder that recapitulated important features of human WM. However, the BCL2 + IL6 + AID - model also exhibited shortcomings, such as low serum IgM levels and histopathological changes not seen in patients with WM, collectively indicating that further refinements of the model are required to achieve better correlations with disease characteristics of WM.
Databáze: MEDLINE
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