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IL6Myc mouse is an immunocompetent model for the development of aggressive multiple myeloma
Journal article   Open access   Peer reviewed

IL6Myc mouse is an immunocompetent model for the development of aggressive multiple myeloma

Michael D Pisano, Fumou Sun, Yan Cheng, Deepak Parashar, Vivian Zhou, Xuefang Jing, Ramakrishna Sompallae, Jenica Abrudan, Michael T Zimmermann, Angela Mathison, …
Haematologica (Roma), Vol.108(12), pp.3372-3383
12/2023
DOI: 10.3324/haematol.2022.282538
PMCID: PMC10690922
PMID: 37439384
url
https://doi.org/10.3324/haematol.2022.282538View
Published (Version of record) Open Access

Abstract

Multiple Myeloma (MM) is a plasma-cell neoplasm originating in the bone marrow and is the second most common blood cancer in the United States. One challenge in understanding the pathogenesis of MM and improving treatment is a lack of immunocompetent mouse models. We previously developed the IL6Myc mouse that generates plasmacytomas at 100% penetrance that phenotypically resemble aggressive MM. Using comprehensive genomic analysis, we found that the IL6Myc tumors resemble aggressive MM by RNA and protein expression. We also found that IL6Myc tumors accumulated fusions and missense mutations in genes that overlap significantly with human myeloma, indicating that the mouse is good model for studying disease etiology. Lastly, we derived cell lines from IL6Myc tumors that express cell-surface markers typical of MM and readily engraft into mice, home to the bone marrow, and induce osteolytic disease. The cell lines may be useful in developing immunotherapies directed against BAFF-R and TACI, though not BCMA, and may also be a good model for studying dexamethasone resistance. These data indicate that the IL6Myc model is useful for studying development of aggressive MM and for developing new treatments against such forms of the disease.

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