A novel rapid-onset high-penetrance plasmacytoma mouse model driven by deregulation of cMYC cooperating with KRAS12V in BALB/c mice

Y. Hu, M. Zheng, R. Gali, Z. Tian, Gullu Gorgun, N. C. Munshi, C. S. Mitsiades, K. C. Anderson

Research output: Contribution to journalArticle

7 Citations (Scopus)

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.

Original languageEnglish (US)
Article numbere156
JournalBlood Cancer Journal
Volume3
Issue number11
DOIs
StatePublished - 2013
Externally publishedYes

Fingerprint

Plasmacytoma
Penetrance
Plasma Cells
Immunoglobulin M
Plasma Cell Neoplasms
B-Lymphocytes
Immunoglobulin D
Multiple Myeloma
Transcriptome
Genes
Immunoglobulins
Neoplasms
Spleen
Biomarkers
Bone Marrow
Liver

Keywords

  • BALB/c mouse
  • CMYC
  • KRAS12V
  • Multiple myeloma (MM)
  • Plasmacytoma
  • Retroviral transduction and transplantation

ASJC Scopus subject areas

  • Oncology
  • Hematology

Cite this

A novel rapid-onset high-penetrance plasmacytoma mouse model driven by deregulation of cMYC cooperating with KRAS12V in BALB/c mice. / Hu, Y.; Zheng, M.; Gali, R.; Tian, Z.; Gorgun, Gullu; Munshi, N. C.; Mitsiades, C. S.; Anderson, K. C.

In: Blood Cancer Journal, Vol. 3, No. 11, e156, 2013.

Research output: Contribution to journalArticle

Hu, Y. ; Zheng, M. ; Gali, R. ; Tian, Z. ; Gorgun, Gullu ; Munshi, N. C. ; Mitsiades, C. S. ; Anderson, K. C. / A novel rapid-onset high-penetrance plasmacytoma mouse model driven by deregulation of cMYC cooperating with KRAS12V in BALB/c mice. In: Blood Cancer Journal. 2013 ; Vol. 3, No. 11.
@article{a2049ef8349147988bc14c8285bfae9f,
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.",
keywords = "BALB/c mouse, CMYC, KRAS12V, Multiple myeloma (MM), Plasmacytoma, Retroviral transduction and transplantation",
author = "Y. Hu and M. Zheng and R. Gali and Z. Tian and Gullu Gorgun and Munshi, {N. C.} and Mitsiades, {C. S.} and Anderson, {K. C.}",
year = "2013",
doi = "10.1038/bcj.2013.53",
language = "English (US)",
volume = "3",
journal = "Blood Cancer Journal",
issn = "2044-5385",
publisher = "Nature Publishing Group",
number = "11",

}

TY - JOUR

T1 - A novel rapid-onset high-penetrance plasmacytoma mouse model driven by deregulation of cMYC cooperating with KRAS12V in BALB/c mice

AU - Hu, Y.

AU - Zheng, M.

AU - Gali, R.

AU - Tian, Z.

AU - Gorgun, Gullu

AU - Munshi, N. C.

AU - Mitsiades, C. S.

AU - Anderson, K. C.

PY - 2013

Y1 - 2013

N2 - 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.

AB - 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.

KW - BALB/c mouse

KW - CMYC

KW - KRAS12V

KW - Multiple myeloma (MM)

KW - Plasmacytoma

KW - Retroviral transduction and transplantation

UR - http://www.scopus.com/inward/record.url?scp=84888413607&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84888413607&partnerID=8YFLogxK

U2 - 10.1038/bcj.2013.53

DO - 10.1038/bcj.2013.53

M3 - Article

C2 - 24185503

AN - SCOPUS:84888413607

VL - 3

JO - Blood Cancer Journal

JF - Blood Cancer Journal

SN - 2044-5385

IS - 11

M1 - e156

ER -