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Murine mantle cell lymphoma model cell line

Leukemia volume 27, pages 1592–1594 (2013)Cite this article

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Mantle cell lymphoma (MCL)1 is characterized by dysregulated expression of cyclin D1 due to the cytogenetic translocation t(11;14)(q13;q32).2 Cyclin D1 interaction with cyclin-dependent kinases (cdk) drives cells through the G1–S checkpoint. Nonetheless, cyclin D1 overexpression in mouse B cells is not sufficient to induce lymphoma and cyclin D1 is necessary, but not sufficient, to produce MCL.3 While therapeutic advances have prolonged survival in MCL,4 with many novel agents in development, optimizing combinations would benefit from an animal model. MCL cell lines generally represent blastoid or atypical variants.5 Two recently reported mouse models of blastoid MCL, one based on interleukin-14/myc double transgenics,6 the other on combined abnormalities of INK4A and myc,7 may provide biological insights and testing for blastoid MCL. Transgenic mice expressing cyclin D1 in B cells are healthy.3 We previously demonstrated that these mice do develop lymphoma with MCL characteristics if their immune system is non-specifically stimulated by pristane when they are older.8 This system can provide biologic insights into genetic events cooperating with cyclin D1.9 Unfortunately, the aging requirement makes this model cumbersome for therapeutic testing. Here we report that the FC-muMCL1 cell line established from a pristane-induced lymphoma, grows in young syngeneic mice, has associated immune cell infiltration, and provides a means to test novel targeted therapies against lymphomas constitutively overexpressing cyclin D1.10

FC-muMCL1 originated from splenocytes of a 1-year-old male Eμ-cyclin D1 transgenic C57Bl6 mouse injected intraperitoneally with pristane monthly × 3 as previously described.8 Initially cultured in RPMI 1640+20% heat-inactivated fetal bovine serum (FBS), 2 mM glutamine/l, 100 units/ml penicillin, 100 g/ml streptomycin, 1 mM Na-pyruvate (Sigma-Aldrich, St Louis, MO, USA), 0.1 mM non-essential amino acids (Cellgro, Mediatech Inc., Manassas, VA, USA), supplemented with 8 μg/ml adenosine, 8.5 μg/ml guanosine, 7.3 μg/ml uridine, 7.3 μg/ml cytidine, 2.4 μg/ml thymidine, 25 μg/ml insulin, 10 μg/ml transferrin, 0.2 nM T3 and 100 μM mercaptoethanolamine, eventually media was changed to RPMI1640+15% FBS without supplements. Cells treated with rapamycin or bortezomib were analyzed for growth by MTS assay and for apoptosis by annexin V-propidium iodide staining and flow cytometry as before.11 Flow cytometric immunophenotyping for B220 (CD45), CD19, CD23 and CD5, and for IgM, IgD, κ and λ was performed as before.11

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References

  1. Harris N, Jaffe E, Stein H, Banks P, Chan J, Cleary M et al. A revised European-American classification of lymphoid neoplasms: a proposal from the International Lymphoma Study Group. Blood 1994; 84: 1361–1392.

    CAS  PubMed  Google Scholar 

  2. Williams ME, Swerdlow SH . Cyclin D1 overexpression in non-Hodgkin's lymphoma with chromosome 11 bcl-1 rearrangement. Ann Oncol 1994; 5 (Suppl 1): 71–73.

    Article  PubMed  Google Scholar 

  3. Bodrug SEWB, Bath ML, Lindeman GJ, Harris AW, Adams JM . Cyclin D1 transgene impedes lymphocyte maturation and collaborates in lymphomagenesis with the myc gene. EMBO J 1994; 13: 2124–2130.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  4. Herrmann A, Hoster E, Zwingers T, Brittinger G, Engelhard M, Meusers P et al. Improvement of overall survival in advanced stage mantle cell lymphoma. J Clin Oncol 2009; 27: 511–518.

    Article  PubMed  Google Scholar 

  5. Drexler HG, MacLeod RA . Mantle cell lymphoma-derived cell lines: unique research tools. Leuk Res 2006; 30: 911–913.

    Article  PubMed  Google Scholar 

  6. Ford RJ, Shen L, Lin-Lee YC, Pham LV, Multani A, Zhou H-J et al. Development of a murine model for blastoid variant mantle-cell lymphoma. Blood 2007; 109: 4899–4906.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  7. Vincent-Fabert C, Fiancette R, Rouaud P, Baudet C, Truffinet V, Magnone V et al. A defect of the INK4-Cdk4 checkpoint and Myc collaborate in blastoid mantle cell lymphoma-like lymphoma formation in mice. Am J Pathol 2012; 180: 1688–1701.

    Article  CAS  PubMed  Google Scholar 

  8. Smith MR, Joshi I, Jin F, Al-Saleem T . Murine model for mantle cell lymphoma. Leukemia 2006; 20: 891–893.

    Article  CAS  PubMed  Google Scholar 

  9. Bradley SV, Smith MR, Hyun TS, Lucas PC, Li L, Antonuk D et al. Aberrant Huntingtin interacting protein 1 in lymphoid malignancies. Cancer Res 2007; 67: 8923–8931.

    Article  CAS  PubMed  Google Scholar 

  10. Cheng F, Wang H, Horna P, Wang Z, Shah B, Sahakian E et al. Stat3 inhibition augments the immunogenicity of B-cell lymphoma cells, leading to effective antitumor immunity. Cancer Res 2012; 72: 4440–4448.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  11. Smith MR, Jin F, Joshi I . Enhanced efficacy of therapy with antisense BCL-2 oligonucleotides plus anti-CD20 monoclonal antibody in scid mouse/human lymphoma xenografts. Mol Cancer Ther 2004; 3: 1693–1699.

    CAS  PubMed  Google Scholar 

  12. Testa JR, Getts LA, Salazar H, Liu Z, Handel LM, Godwin AK et al. Spontaneous transformation of rat ovarian surface epithelial cells results in well to poorly differentiated tumors with a parallel range of cytogenetic complexity. Cancer Res 1994; 54: 2778–2784.

    CAS  PubMed  Google Scholar 

  13. Timakhov RA, Tan Y, Rao M, Liu Z, Altomare DA, Pei J et al. Recurrent chromosomal rearrangements implicate oncogenes contributing to T-cell lymphomagenesis in Lck-MyrAkt2 transgenic mice. Genes Chromosomes Cancer 2009; 48: 786–794.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  14. Xiao C, Calado DP, Galler G, Thai TH, Patterson HC, Wang J et al. MiR-150 controls B cell differentiation by targeting the transcription factor c-Myb. Cell 2007; 131: 146–159.

    Article  CAS  PubMed  Google Scholar 

  15. Wang M, Zhang L, Han X, Yang J, Qian J, Hong S et al. A severe combined immunodeficient-hu in vivo mouse model of human primary mantle cell lymphoma. Clin Cancer Res 2008; 14: 2154–2160.

    Article  CAS  PubMed  Google Scholar 

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Acknowledgements

This work was supported in part by NCI P30 CA006927, utilizing Fox Chase Cancer Center Core Facilities in Genomics, Flow Cytometry, Bioinformatics and the Laboratory Animal Facility. Also, supported in part by Leukemia Lymphoma Society of America Translational Grant no. 6187-03; The Lymphoma Foundation; American Cancer Society Institutional Research Grant; and Aventis Pharmaceuticals. Additional funding was from the Janice Charach Epstein Research Fund and Lester Smith Research Fund of Fox Chase Cancer Center.

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  1. M R Smith

    Present address: 5Current address: Cleveland Clinic, Cleveland, OH, USA,

Authors and Affiliations

  1. Department of Medical Oncology, Fox Chase Cancer Center, Philadelphia, PA,

    M R Smith, I Joshi & F Jin

  2. Cancer Biology Program,

    J Pei & J R Testa

  3. Department of Bioinformatics,

    M Slifker

  4. Department of Pathology, Fox Chase Cancer Center, Philadelphia, PA, USA,

    T Al-Saleem

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Correspondence to M R Smith.

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Smith, M., Joshi, I., Pei, J. et al. Murine mantle cell lymphoma model cell line. Leukemia 27, 1592–1594 (2013). https://doi.org/10.1038/leu.2012.370

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