title: A novel rapid-onset high-penetrance plasmacytoma mouse model driven by deregulation of cMYC cooperating with KRAS12V in BALB/c mice.
abstract: Our goal is to develop a rapid and scalable system for functionally evaluating deregulated genes in multiple myeloma (MM). Here, we forcibly expressed human cMYC and KRAS12V in mouse T2 B cells (IgM(+)B220(+)CD38(+)IgD(+)) using retroviral transduction and transplanted these cells into lethally irradiated recipient mice. Recipients developed plasmacytomas with short onset (70 days) and high penetrance, whereas neither cMYC nor KRAS12V alone induced disease in recipient mice. Tumor cell morphology and cell surface biomarkers (CD138(+)B220(-)IgM(-)GFP(+)) indicate a plasma cell neoplasm. Gene set enrichment analysis further confirms that the tumor cells have a plasma cell gene expression signature. Plasmacytoma cells infiltrated multiple loci in the bone marrow, spleen and liver; secreted immunoglobulins; and caused glomerular damage. Our findings therefore demonstrate that deregulated expression of cMYC with KRAS12V in T2 B cells rapidly generates a plasma cell disease in mice, suggesting utility of this model both to elucidate molecular pathogenesis and to validate novel targeted therapies.
authors.affiliation: Department of Medical Oncology, LeBow Institute for Myeloma Therapeutics and Jerome Lipper Center for Multiple Myeloma Research, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA, USA.
authors.forename: Y
authors.initials: Y
authors.lastname: Hu
authors.forename: M
authors.initials: M
authors.lastname: Zheng
authors.forename: R
authors.initials: R
authors.lastname: Gali
authors.forename: Z
authors.initials: Z
authors.lastname: Tian
authors.forename: G
authors.initials: G
authors.lastname: Topal Görgün
authors.forename: N C
authors.initials: NC
authors.lastname: Munshi
authors.forename: C S
authors.initials: CS
authors.lastname: Mitsiades
authors.forename: K C
authors.initials: KC
authors.lastname: Anderson