Transgenic mouse model of IgM + lymphoproliferative disease mimicking Waldenström macroglobulinemia

V S Tompkins; R Sompallae; T R Rosean; S Walsh; M Acevedo; A L Kovalchuk; S-S Han; X Jing; C Holman; J E Rehg; S Herms; J S Sunderland; H C Morse; S Janz

doi:10.1038/bcj.2016.95

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Transgenic mouse model of IgM + lymphoproliferative disease mimicking Waldenström macroglobulinemia

Journal article

Open access

Peer reviewed

Transgenic mouse model of IgM + lymphoproliferative disease mimicking Waldenström macroglobulinemia

V S Tompkins, R Sompallae, T R Rosean, S Walsh, M Acevedo, A L Kovalchuk, S-S Han, X Jing, C Holman, J E Rehg, …

Blood cancer journal (New York), Vol.6(11), pp.e488-e488

11/04/2016

DOI: 10.1038/bcj.2016.95

PMCID: PMC5148059

PMID: 27813533

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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 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.

Waldenstrom Macroglobulinemia - blood

Humans

Mice, Transgenic

Lymphoproliferative Disorders - genetics

Lymphoproliferative Disorders - immunology

Immunoglobulin M - immunology

Lymphoproliferative Disorders - pathology

Lymphoproliferative Disorders - blood

Waldenstrom Macroglobulinemia - pathology

Waldenstrom Macroglobulinemia - immunology

Animals

Immunoglobulin M - blood

Mice

Waldenstrom Macroglobulinemia - genetics

Disease Models, Animal

Immunoglobulin M - genetics

Details

Title: Subtitle: Transgenic mouse model of IgM + lymphoproliferative disease mimicking Waldenström macroglobulinemia
Creators: V S Tompkins - Department of Pathology, Iowa Institute of Human Genetics, University of Iowa Roy J. and Lucille A. Carver College of Medicine, Iowa City, IA, USA
R Sompallae - Bioinformatics Division, Iowa Institute of Human Genetics, University of Iowa Roy J. and Lucille A. Carver College of Medicine, Iowa City, IA, USA
T R Rosean - Department of Pathology, Iowa Institute of Human Genetics, University of Iowa Roy J. and Lucille A. Carver College of Medicine, Iowa City, IA, USA
S Walsh - Department of Radiology, University of Iowa Roy J. and Lucille A. Carver College of Medicine, Iowa City, IA, USA
M Acevedo - Department of Radiology, University of Iowa Roy J. and Lucille A. Carver College of Medicine, Iowa City, IA, USA
A L Kovalchuk - Virology and Cellular Immunology Section, Laboratory of Immunogenetics, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Rockville, MD, USA
S-S Han - Department of Pathology, Iowa Institute of Human Genetics, University of Iowa Roy J. and Lucille A. Carver College of Medicine, Iowa City, IA, USA
X Jing - Department of Pathology, Iowa Institute of Human Genetics, University of Iowa Roy J. and Lucille A. Carver College of Medicine, Iowa City, IA, USA
C Holman - Department of Pathology, Iowa Institute of Human Genetics, University of Iowa Roy J. and Lucille A. Carver College of Medicine, Iowa City, IA, USA
J E Rehg - Department of Pathology, St Jude Children's Research Hospital, Memphis, TN, USA
S Herms - International Waldenstrom's Macroglobulinemia Foundation, Sarasota, FL, USA
J S Sunderland - Department of Radiology, University of Iowa Roy J. and Lucille A. Carver College of Medicine, Iowa City, IA, USA
H C Morse - Virology and Cellular Immunology Section, Laboratory of Immunogenetics, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Rockville, MD, USA
S Janz - Department of Pathology, Iowa Institute of Human Genetics, University of Iowa Roy J. and Lucille A. Carver College of Medicine, Iowa City, IA, USA
Resource Type: Journal article
Publication Details: Blood cancer journal (New York), Vol.6(11), pp.e488-e488
DOI: 10.1038/bcj.2016.95
PMID: 27813533
PMCID: PMC5148059
NLM abbreviation: Blood Cancer J
ISSN: 2044-5385
eISSN: 2044-5385
Grant note: R01 CA151354 / NCI NIH HHS T32 HL007344 / NHLBI NIH HHS T32 AI007485 / NIAID NIH HHS P30 CA086862 / NCI NIH HHS
Language: English
Date published: 11/04/2016
Academic Unit: Radiology; Stead Family Department of Pediatrics; Pathology; Physics and Astronomy; Radiation Oncology
Record Identifier: 9984083886802771

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