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.

  • Brief Communication
  • Published:

Prognostic significance of interphase FISH in monoclonal gammopathy of undetermined significance

Leukemia volume 32, pages 1811–1815 (2018)Cite this article

Subjects

Monoclonal gammopathy of undetermined significance (MGUS) is a clonal plasma cell (PC) disorder characterized by the presence in serum of monoclonal protein <3 g/dL and bone marrow PC (BMPC) percentage <10% [1]. Patients with MGUS have a 1% per year risk of developing multiple myeloma (MM), AL amyloidosis or other lymphoproliferative disorders [2]. Interphase fluorescence in situ hybridization (FISH) testing of BMPCs identifies recurring cytogenetic abnormalities in patients with PC dyscrasias and is of prognostic importance in MM, SMM and AL amyloidosis [3,4,5,6,7]. High-risk abnormalities [t(4;14), del(17p), 1q gain] are associated with shorter time to progression (TTP) in smoldering multiple myeloma (SMM) [5, 6]. The presence of hyperdiploidy (trisomies) in patients with SMM is also associated with shorter TTP [5, 6]. Previous studies detected abnormalities similar to those seen in MM in patients with MGUS [8,9,10,11,12]. The prognostic importance of these abnormalities is not known. In this context, we aimed to define their impact on TTP in MGUS.

We reviewed the records of all patients with MGUS, seen at Mayo Clinic, Rochester, who underwent FISH testing between 2004 and 2014. Patients met the criteria for MGUS at FISH testing [1]. We collected data regarding the laboratory tests and progression of MGUS (defined as evolution to SMM, MM or AL amyloidosis or initiation of therapy for PC dyscrasia). TTP was defined as the duration from FISH testing to progression. Patients were censored if they had not progressed at last follow-up. Patients who had not progressed at the time of death were censored on the date of death. Overall survival (OS) was defined as the duration from FISH testing to death or last follow-up, patients being censored if they were alive. TTP and OS were estimated using the Kaplan Meier method. We used Cox proportional hazards model to evaluate the factors affecting TTP. A two-tailed p-value<0.05 was considered significant for all statistical tests. JMP® Pro 13.0 (SAS Institute Inc., Cary, NC, USA) was used for statistical analysis. The Mayo Clinic Institutional Review Board approved the study and it was conducted in accordance with the Declaration of Helsinki and the Health Insurance Portability and Accountability Act guidelines of 1996.

This is a preview of subscription content, access via your institution

Access options

Buy this article

  • Purchase on Springer Link
  • Instant access to full article PDF
Buy now

Prices may be subject to local taxes which are calculated during checkout

Fig. 1

References

  1. Rajkumar SV, Dimopoulos MA, Palumbo A, Blade J, Merlini G, Mateos MV, et al. International Myeloma Working Group updated criteria for the diagnosis of multiple myeloma. Lancet Oncol. 2014;15:e538–48.

    Article  PubMed  Google Scholar 

  2. Kyle RA, Therneau TM, Rajkumar SV, Offord JR, Larson DR, Plevak MF, et al. A long-term study of prognosis in monoclonal gammopathy of undetermined significance. N Engl J Med. 2002;346:564–9.

    Article  PubMed  Google Scholar 

  3. Mikhael JR, Dingli D, Roy V, Reeder CB, Buadi FK, Hayman SR, et al. Management of newly diagnosed symptomatic multiple myeloma: updated Mayo Stratification of Myeloma and Risk-Adapted Therapy (mSMART) consensus guidelines 2013. Mayo Clin Proc. 2013;88:360–76.

    Article  PubMed  Google Scholar 

  4. Chng WJ, Dispenzieri A, Chim CS, Fonseca R, Goldschmidt H, Lentzsch S, et al. IMWG consensus on risk stratification in multiple myeloma. Leukemia. 2014;28:269–77.

    Article  PubMed  CAS  Google Scholar 

  5. Rajkumar SV, Gupta V, Fonseca R, Dispenzieri A, Gonsalves WI, Larson D, et al. Impact of primary molecular cytogenetic abnormalities and risk of progression in smoldering multiple myeloma. Leukemia. 2013;27:1738–44.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  6. Neben K, Jauch A, Hielscher T, Hillengass J, Lehners N, Seckinger A, et al. Progression in smoldering myeloma is independently determined by the chromosomal abnormalities del(17p), t(4;14), Gain 1q, hyperdiploidy, and tumor load. J Clin Oncol. 2013;31:4325–32.

    Article  PubMed  Google Scholar 

  7. Warsame R, Kumar SK, Gertz MA, Lacy MQ, Buadi FK, Hayman SR, et al. Abnormal FISH in patients with immunoglobulin light chain amyloidosis is a risk factor for cardiac involvement and for death. Blood Cancer J. 2015;5:e310.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  8. Drach J, Angerler J, Schuster J, Rothermundt C, Thalhammer R, Haas OA, et al. Interphase fluorescence in situ hybridization identifies chromosomal abnormalities in plasma cells from patients with monoclonal gammopathy of undetermined significance. Blood. 1995;86:3915–21.

    PubMed  CAS  Google Scholar 

  9. Zandecki M, Obein V, Bernardi F, Soenen V, Flactif M, Lai JL, et al. Monoclonal gammopathy of undetermined significance: chromosome changes are a common finding within bone marrow plasma cells. Br J Haematol. 1995;90:693–6.

    Article  PubMed  CAS  Google Scholar 

  10. Zandecki M, Lai JL, Genevieve F, Bernardi F, Volle-Remy H, Blanchet O, et al. Several cytogenetic subclones may be identified within plasma cells from patients with monoclonal gammopathy of undetermined significance, both at diagnosis and during the indolent course of this condition. Blood. 1997;90:3682–90.

    PubMed  CAS  Google Scholar 

  11. Fonseca R, Bailey RJ, Ahmann GJ, Rajkumar SV, Hoyer JD, Lust JA, et al. Genomic abnormalities in monoclonal gammopathy of undetermined significance. Blood. 2002;100:1417–24.

    PubMed  CAS  Google Scholar 

  12. Brousseau M, Leleu X, Gerard J, Gastinne T, Godon A, Genevieve F, et al. Hyperdiploidy is a common finding in monoclonal gammopathy of undetermined significance and monosomy 13 is restricted to these hyperdiploid patients. Clin Cancer Res. 2007;13:6026–31.

    Article  PubMed  CAS  Google Scholar 

  13. Kumar S, Fonseca R, Ketterling RP, Dispenzieri A, Lacy MQ, Gertz MA, et al. Trisomies in multiple myeloma: impact on survival in patients with high-risk cytogenetics. Blood. 2012;119:2100–5.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  14. Avet-Loiseau H, Facon T, Daviet A, Godon C, Rapp MJ, Harousseau JL, et al. 14q32 translocations and monosomy 13 observed in monoclonal gammopathy of undetermined significance delineate a multistep process for the oncogenesis of multiple myeloma. Intergroupe Francophone du Myelome. Cancer Res. 1999;59:4546–50.

    PubMed  CAS  Google Scholar 

  15. Rajkumar SV, Kyle RA, Therneau TM, Melton LJ 3rd, Bradwell AR, Clark RJ, et al. Serum free light chain ratio is an independent risk factor for progression in monoclonal gammopathy of undetermined significance. Blood. 2005;106:812–7.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

Download references

Acknowledgements

This work was supported in part by grants from the National Cancer Institute (CA168762 and CA107476).

Author information

Authors and Affiliations

  1. Division of Hematology, Mayo Clinic, Rochester, Minnesota, USA

    Arjun Lakshman, Shilpa Paul, S. Vincent Rajkumar, Angela Dispenzieri, Morie A Gertz, Francis K. Buadi, Martha Q. Lacy, David Dingli, Amie L. Fonder, Suzanne R. Hayman, Miriam A. Hobbs, Wilson I. Gonsalves, Yi Lisa Hwa, Prashant Kapoor, Nelson Leung, Ronald S. Go, Yi Lin, Taxiarchis V. Kourelis, Rahma Warsame, John A. Lust, Stephen J. Russell, Steven R. Zeldenrust, Robert A. Kyle & Shaji K. Kumar

  2. Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, Minnesota, USA

    Rhett P. Ketterling & Patricia T. Greipp

Authors
  1. Arjun Lakshman
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Shilpa Paul
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. S. Vincent Rajkumar
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Rhett P. Ketterling
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Patricia T. Greipp
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Angela Dispenzieri
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Morie A Gertz
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Francis K. Buadi
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. Martha Q. Lacy
    View author publications

    You can also search for this author in PubMed Google Scholar

  10. David Dingli
    View author publications

    You can also search for this author in PubMed Google Scholar

  11. Amie L. Fonder
    View author publications

    You can also search for this author in PubMed Google Scholar

  12. Suzanne R. Hayman
    View author publications

    You can also search for this author in PubMed Google Scholar

  13. Miriam A. Hobbs
    View author publications

    You can also search for this author in PubMed Google Scholar

  14. Wilson I. Gonsalves
    View author publications

    You can also search for this author in PubMed Google Scholar

  15. Yi Lisa Hwa
    View author publications

    You can also search for this author in PubMed Google Scholar

  16. Prashant Kapoor
    View author publications

    You can also search for this author in PubMed Google Scholar

  17. Nelson Leung
    View author publications

    You can also search for this author in PubMed Google Scholar

  18. Ronald S. Go
    View author publications

    You can also search for this author in PubMed Google Scholar

  19. Yi Lin
    View author publications

    You can also search for this author in PubMed Google Scholar

  20. Taxiarchis V. Kourelis
    View author publications

    You can also search for this author in PubMed Google Scholar

  21. Rahma Warsame
    View author publications

    You can also search for this author in PubMed Google Scholar

  22. John A. Lust
    View author publications

    You can also search for this author in PubMed Google Scholar

  23. Stephen J. Russell
    View author publications

    You can also search for this author in PubMed Google Scholar

  24. Steven R. Zeldenrust
    View author publications

    You can also search for this author in PubMed Google Scholar

  25. Robert A. Kyle
    View author publications

    You can also search for this author in PubMed Google Scholar

  26. Shaji K. Kumar
    View author publications

    You can also search for this author in PubMed Google Scholar

Contributions

AL and SP collected and analyzed the data, wrote the first draft, and approved the final version of the manuscript; SVR, AD, MAG, FKB, MQL, DD, ALF, SRH, MAH, WIG, YLH, PK, NL, RSG, YL, TVK, RW, JAL, SJR and SRZ performed patient management, revised the manuscript critically, and approved the final version of the manuscript; RPK and PTG performed the FISH testing, revised the manuscript critically, and approved the final version of the manuscript; RAK performed patients’ follow-up, revised the manuscript critically, and participated in final data analysis and approval of the final version of the manuscript; and SKK designed the study, analyzed the data, wrote the first draft, approved the final version of the manuscript, and performed patient management.

Corresponding author

Correspondence to Shaji K. Kumar.

Ethics declarations

Conflict of interest

AD: Celgene, Takeda, Pfizer, Prothena and Alnylam (research funding). MAG: Johnson and Johnson (honoraria). PK: Takeda, Amgen and Sanofi (research funding) and Celgene and Sanofi (consulting fees). YL: Janssen (research funding). SKK: Abbvie, Celgene, Janssen, Merck, Novartis, Roche, Sanofi, and Takeda (research funding) and Skyline Diagnostics (honoraria). The remaining authors declare that they have no conflict of interest.

Electronic supplementary material

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Lakshman, A., Paul, S., Rajkumar, S.V. et al. Prognostic significance of interphase FISH in monoclonal gammopathy of undetermined significance. Leukemia 32, 1811–1815 (2018). https://doi.org/10.1038/s41375-018-0030-3

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/s41375-018-0030-3

This article is cited by

Search

Advanced search

Quick links