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.

  • Letter to the Editor
  • Published:

Prognostic value of Cyclin D2 mRNA expression in newly diagnosed multiple myeloma treated with high-dose chemotherapy and tandem autologous stem cell transplantations

Leukemia volume 20, pages 1288–1290 (2006)Cite this article

Multiple myeloma (MM) is a neoplasm of terminally differentiated B cells characterized by clonal expansion of malignant plasma cells. High-dose therapy with melphalan supported by transplant(s) has become a standard care, especially for patients under the age of 65 years, and can prolong survival; however, at least 70% of patients relapse and survival ranges from less than a few months to greater than 10 years.1 The prognosis of patients with myeloma is currently best estimated using the clinical parameters such as β-2-microglobulin, albumin and LDH, cytogenetics and recently gene expression profiling1, 2

Through gene expression profiling (GEP) studies of a large population of newly diagnosed patients with myeloma, we have reported that most myeloma tumors dysregulate at least one of the three D-type cyclins and these events are mutually exclusive.3, 4 CCND2 is normally expressed in B-lymphocytes, especially in activated cells, but not in normal plasma cells. High expression of CCND2 is observed in tumors with immunoglobulin heavy-chain gene locus translocations involving c-MAF, MAFB or FGFR3/MMSET, but also importantly a substantial subset of tumors lacking these translocations.3 Both c-MAF and MAFB are basic/leucine zipper transcription factors of the large-MAF proto-oncogene family. Hurt et al.5 showed that CCND2 is transcriptionally activated by c-MAF in MM. It is thought that MAFB may also trans-activate CCND2 expression. The mechanism of CCND2 overexpression in cases with FGFR3/MMSET-activating translocations is unknown.

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

Figure 1

Accession codes

Accessions

GenBank/EMBL/DDBJ

References

  1. Barlogie B, Shaughnessy J, Tricot G, Jacobson J, Zangari M, Anaissie E et al. Treatment of multiple myeloma. Blood 2004; 103: 20–32.

    Article  CAS  Google Scholar 

  2. Stewart AK, Fonseca R . Prognostic and therapeutic significance of myeloma genetics and gene expression profiling. J Clin Oncol 2005; 23: 6339–6344.

    Article  CAS  Google Scholar 

  3. Bergsagel P, Kuehl W, Zhan F, Sawyer J, Barlogie B, Shaughnessy J . Cyclin D dysregulation: an early and unifying pathogenic event in multiple myeloma. Blood 2005; 106: 296–303.

    Article  CAS  Google Scholar 

  4. Agnelli L, Bicciato S, Mattioli M, Fabris S, Intini D, Verdelli D et al. Molecular classification of multiple myeloma: a distinct transcriptional profile characterizes patients expressing CCND1 and negative for 14q32 translocations. J Clin Oncol 2005; 23: 7296–7306.

    Article  CAS  Google Scholar 

  5. Hurt EM, Wiestner A, Rosenwald A, Shaffer AL, Campo E, Grogan T et al. Overexpression of c-maf is a frequent oncogenic event in multiple myeloma that promotes proliferation and pathological interactions with bone marrow stroma. Cancer Cell 2004; 5: 191–199.

    Article  CAS  Google Scholar 

  6. Soverini S, Cavo M, Cellini C, Terragna C, Zamagni E, Ruggeri D et al. Cyclin D1 overexpression is a favorable prognostic variable for newly diagnosed multiple myeloma patients treated with high-dose chemotherapy and single or double autologous transplantation. Blood 2003; 102: 1588–1594.

    Article  CAS  Google Scholar 

  7. Malumbres M, Barbacid M . To cycle or not to cycle: a critical decision in cancer. Nat Rev Cancer 2001; 1: 222–231.

    Article  CAS  Google Scholar 

  8. Ely S, Di Liberto M, Niesvizky R, Baughn LB, Cho HJ, Hatada EN et al. Mutually exclusive cyclin-dependent kinase 4/cyclin D1 and cyclin-dependent kinase 6/cyclin D2 pairing inactivates retinoblastoma protein and promotes cell cycle dysregulation in multiple myeloma. Cancer Res 2005; 65: 11345–11353.

    Article  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Donna D and Donald M Lambert Laboratory of Myeloma Genetics, Myeloma Institute for Research and Therapy, University of Arkansas for Medical Sciences, Little Rock, AR, USA

    I Hanamura, Y Huang, F Zhan, B Barlogie & J Shaughnessy Jr

Authors
  1. I Hanamura
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Y Huang
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. F Zhan
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. B Barlogie
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. J Shaughnessy Jr
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to J Shaughnessy Jr.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Hanamura, I., Huang, Y., Zhan, F. et al. Prognostic value of Cyclin D2 mRNA expression in newly diagnosed multiple myeloma treated with high-dose chemotherapy and tandem autologous stem cell transplantations. Leukemia 20, 1288–1290 (2006). https://doi.org/10.1038/sj.leu.2404253

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/sj.leu.2404253

This article is cited by

Search

Advanced search

Quick links