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Transgenic mouse model of IgM lymphoproliferative disease mimicking Waldenström macroglobulinemia. Blood Cancer J 2016 11 04;6(11):e488

Date

11/05/2016

Pubmed ID

27813533

Pubmed Central ID

PMC5148059

DOI

10.1038/bcj.2016.95

Abstract

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-hIL6, on the genetic background of activation-induced cytidine deaminase (AID) deficiency. We designated these mice BCL2IL6AID 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 BCL2IL6AID 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.

Author List

Tompkins VS, Sompallae R, Rosean TR, Walsh S, Acevedo M, Kovalchuk AL, Han SS, Jing X, Holman C, Rehg JE, Herms S, Sunderland JS, Morse HC, Janz S

Author

Siegfried Janz MD Professor in the Medicine department at Medical College of Wisconsin




MESH terms used to index this publication - Major topics in bold

Animals
Disease Models, Animal
Humans
Immunoglobulin M
Lymphoproliferative Disorders
Mice
Mice, Transgenic
Waldenstrom Macroglobulinemia
jenkins-FCD Prod-399 190a069c593fb5498b7fcd942f44b7bc9cdc7ea1