A transgenic mouse model of plasma cell malignancy shows phenotypic, cytogenetic, and gene expression heterogeneity similar to human multiple myeloma

Kristin L. M BOYLAN; Mary A GOSSE; Sarah E STAGGS; Siegfried JANZ; Suzanne GRINDLE; Geoffrey S KANSAS; Brian G VAN NESS

doi:10.1158/0008-5472.CAN-06-3699

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A transgenic mouse model of plasma cell malignancy shows phenotypic, cytogenetic, and gene expression heterogeneity similar to human multiple myeloma

Journal article

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A transgenic mouse model of plasma cell malignancy shows phenotypic, cytogenetic, and gene expression heterogeneity similar to human multiple myeloma

Kristin L. M BOYLAN, Mary A GOSSE, Sarah E STAGGS, Siegfried JANZ, Suzanne GRINDLE, Geoffrey S KANSAS and Brian G VAN NESS

Cancer research (Chicago, Ill.), Vol.67(9), pp.4069-4078

2007

DOI: 10.1158/0008-5472.CAN-06-3699

PMID: 17483317

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Abstract

Multiple myeloma is an incurable plasma cell malignancy for which existing animal models are limited. We have previously shown that the targeted expression of the transgenes c-Myc and Bcl-X(L) in murine plasma cells produces malignancy that displays features of human myeloma, such as localization of tumor cells to the bone marrow and lytic bone lesions. We have isolated and characterized in vitro cultures and adoptive transfers of tumors from Bcl-xl/Myc transgenic mice. Tumors have a plasmablastic morphology and variable expression of CD138, CD45, CD38, and CD19. Spectral karyotyping analysis of metaphase chromosomes from primary tumor cell cultures shows that the Bcl-xl/Myc tumors contain a variety of chromosomal abnormalities, including trisomies, translocations, and deletions. The most frequently aberrant chromosomes are 12 and 16. Three sites for recurring translocations were also identified on chromosomes 4D, 12F, and 16C. Gene expression profiling was used to identify differences in gene expression between tumor cells and normal plasma cells (NPC) and to cluster the tumors into two groups (tumor groups C and D), with distinct gene expression profiles. Four hundred and ninety-five genes were significantly different between both tumor groups and NPCs, whereas 124 genes were uniquely different from NPCs in tumor group C and 204 genes were uniquely different from NPCs in tumor group D. Similar to human myeloma, the cyclin D genes are differentially dysregulated in the mouse tumor groups. These data suggest the Bcl-xl/Myc tumors are similar to a subset of plasmablastic human myelomas and provide insight into the specific genes and pathways underlying the human disease.

Immunopathology

Antineoplastic Agents

Tumors

Hematologic and hematopoietic diseases

Pharmacology. Drug treatments

Leukemias. Malignant lymphomas. Malignant reticulosis. Myelofibrosis

Biological and medical sciences

Immunoglobulinopathies

Medical sciences

Immunodeficiencies. Immunoglobulinopathies

Details

Title: Subtitle: A transgenic mouse model of plasma cell malignancy shows phenotypic, cytogenetic, and gene expression heterogeneity similar to human multiple myeloma
Creators: Kristin L. M BOYLAN - University of Minnesota, Minneapolis, Minnesota, United States
Mary A GOSSE - University of Minnesota, Minneapolis, Minnesota, United States
Sarah E STAGGS - Northwestern University, Chicago, Illinois, United States
Siegfried JANZ - National Cancer Institute. NIH, Bethesda, Maryland, United States
Suzanne GRINDLE - University of Minnesota, Minneapolis, Minnesota, United States
Geoffrey S KANSAS - Northwestern University, Chicago, Illinois, United States
Brian G VAN NESS - University of Minnesota, Minneapolis, Minnesota, United States
Resource Type: Journal article
Publication Details: Cancer research (Chicago, Ill.), Vol.67(9), pp.4069-4078
DOI: 10.1158/0008-5472.CAN-06-3699
PMID: 17483317
NLM abbreviation: Cancer Res
ISSN: 0008-5472
eISSN: 1538-7445
Publisher: American Association for Cancer Research
Language: English
Date published: 2007
Academic Unit: Pathology
Record Identifier: 9984083296602771

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