Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

Diet-induced obesity promotes a myeloma-like condition in vivo

Leukemia volume 29, pages 507–510 (2015)Cite this article

Subjects

Multiple myeloma remains a fatal haematological malignancy associated with clonal plasma cell expansion within the bone marrow, osteolytic bone disease, anaemia and renal failure. In almost all cases, myeloma is preceded by the nonmalignant plasma cell disorder monoclonal gammopathy of undetermined significance (MGUS), characterized by an increase in monoclonal immunoglobulin secretion, <10% plasma cells within the bone marrow and a lack of lytic bone lesions. The mechanisms underlying the pathogenesis of MGUS and progression to myeloma are complex with a major role attributed to the host microenvironment. A loss of host-derived adiponectin is known to promote myeloma development in vivo, both in murine models and in patients with MGUS.1 Adiponectin is inversely linked to obesity, with increasing epidemiological evidence supporting an association between obesity and MGUS or myeloma.2, 3, 4, 5, 6, 7 In the present study, we have combined a well-characterized murine model of myeloma with diet-induced obesity and a genetic model of obesity to determine the effect of increased obesity on myeloma development in vivo.

This is a preview of subscription content

Access options

Buy article

Get time limited or full article access on ReadCube.

$32.00

Buy

All prices are NET prices.

Figure 1
Figure 2

References

  1. Fowler JA, Lwin ST, Drake MT, Edwards JR, Kyle RA, Mundy GR et al. Host-derived adiponectin is tumor-suppressive and a novel therapeutic target for multiple myeloma and the associated bone disease. Blood 2011; 118: 5872–5882.

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  2. Landgren O, Rajkumar SV, Pfeiffer RM, Kyle RA, Katzmann JA, Dispenzieri A et al. Obesity is associated with an increased risk of monoclonal gammopathy of undetermined significance (MGUS) among African-American and Caucasian women. Blood 2010; 116: 1056–1059.

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  3. Wallin A, Larsson SC . Body mass index and risk of multiple myeloma: a meta-analysis of prospective studies. Eur J Cancer 2011; 47: 1606–1615.

    Article  PubMed  Google Scholar 

  4. Carson KR, Bates ML, Tomasson MH . The skinny on obesity and plasma cell myeloma: a review of the literature. Bone Marrow Transplant 2014; 49: 1009–1015.

    CAS  Article  PubMed  Google Scholar 

  5. Teras LR, Kitahara CM, Birmann BM, Hartge PA, Wang SS, Robien K et al. Body size and multiple myeloma mortality: a pooled analysis of 20 prospective studies. Br J Haematol 2014; 166: 667–676.

    Article  PubMed  PubMed Central  Google Scholar 

  6. Hofmann JN, Moore SC, Lim U, Park Y, Baris D, Hollenbeck AR et al. Body mass index and physical activity at different ages and risk of multiple myeloma in the NIH-AARP diet and health study. Am J Epidemiol 2013; 177: 776–786.

    Article  PubMed  PubMed Central  Google Scholar 

  7. Murphy F, Kroll ME, Pirie K, Reeves G, Green J, Beral V . Body size in relation to incidence of subtypes of haematological malignancy in the prospective Million Women Study. Br J Cancer 2013; 108: 2390–2398.

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  8. Radl J, Croese JW, Zurcher C, Van den Enden-Vieveen MH, de Leeuw AM . Animal model of human disease. Multiple myeloma. Am J Pathol 1988; 132: 593–597.

    CAS  PubMed  PubMed Central  Google Scholar 

  9. Fowler JA, Mundy GR, Lwin ST, Edwards CM . Bone marrow stromal cells create a permissive microenvironment for myeloma development: a new stromal role for Wnt inhibitor Dkk1. Cancer Res 2012; 72: 2183–2189.

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  10. Kyle RA, Rajkumar SV . Monoclonal gammopathy of undetermined significance and smoldering multiple myeloma. Hematol Oncol Clin North Am 2007; 21: 1093–1113.

    Article  Google Scholar 

  11. Ng AC, Khosla S, Charatcharoenwitthaya N, Kumar SK, Achenbach SJ, Holets MF et al. Bone microstructural changes revealed by high-resolution peripheral quantitative computed tomography imaging and elevated DKK1 and MIP-1alpha levels in patients with MGUS. Blood 2011; 118: 6529–6534.

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  12. Coleman DL, Hummel KP . The influence of genetic background on the expression of the obese (Ob) gene in the mouse. Diabetologia 1973; 9: 287–293.

    CAS  Article  Google Scholar 

  13. Ribeiro AM, Andrade S, Pinho F, Monteiro JD, Costa M, Lopes C et al. Prostate cancer cell proliferation and angiogenesis in different obese mice models. Int J Exp Pathol 2010; 91: 374–386.

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  14. Georgii-Hemming P, Wiklund HJ, Ljunggren O, Nilsson K . Insulin-like growth factor I is a growth and survival factor in human multiple myeloma cell lines. Blood 1996; 88: 2250–2258.

    CAS  PubMed  Google Scholar 

  15. Beason TS, Chang SH, Sanfilippo KM, Luo S, Colditz GA, Vij R et al. Influence of body mass in dex on survival in veterans with multiple myeloma. Oncologist 2013; 18: 1074–1079.

    Article  PubMed  PubMed Central  Google Scholar 

Download references

Acknowledgements

This work was supported by the National Cancer Institute through R01-CA137116, an American Society of Bone and Mineral Research Career Establishment Award and a Marie Curie Career Integration Grant within the 7th European Community Framework Programme.

Author information

Author notes

  1. S T Lwin and S W Z Olechnowicz: These authors contributed equally to this work.

Authors and Affiliations

  1. Nuffield Department of Surgical Sciences, University of Oxford, Oxford, UK

    S T Lwin, S W Z Olechnowicz & C M Edwards

  2. Nuffield Department of Orthopaedics, Rheumatology and Musculoskeletal Sciences, Botnar Research Centre, University of Oxford, Oxford, UK

    S T Lwin & C M Edwards

  3. Vanderbilt Center for Bone Biology, Vanderbilt University, Nashville, TN, USA

    S T Lwin, J A Fowler & C M Edwards

Authors
  1. S T Lwin
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. S W Z Olechnowicz
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. J A Fowler
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. C M Edwards
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to C M Edwards.

Ethics declarations

Competing interests

The authors declare no conflict of interest.

Additional information

Supplementary Information accompanies this paper on the Leukemia website

Supplementary information

Rights and permissions

Reprints and Permissions

About this article

Verify currency and authenticity via CrossMark

Cite this article

Lwin, S., Olechnowicz, S., Fowler, J. et al. Diet-induced obesity promotes a myeloma-like condition in vivo. Leukemia 29, 507–510 (2015). https://doi.org/10.1038/leu.2014.295

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/leu.2014.295

Further reading

Search

Advanced search

Quick links