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.

  • Original Manuscript
  • Published:

Proteomics

Discrete serum protein signatures discriminate between human retrovirus-associated hematologic and neurologic disease

Leukemia volume 19, pages 1229–1238 (2005)Cite this article

Abstract

The human T-cell leukemia virus type I (HTLV-I) is the causative agent for adult T-cell leukemia (ATL) and HTLV-I-associated myelopathy/tropical spastic paraparesis (HAM/TSP). Approximately 5% of infected individuals will develop either disease and currently there are no diagnostic tools for early detection or accurate assessment of disease state. We have employed high-throughput expression profiling of serum proteins using mass spectrometry to identify protein expression patterns that can discern between disease states of HTLV-I-infected individuals. Our study group consisted of 42 ATL, 50 HAM/TSP, and 38 normal controls. Spectral peaks corresponding to peptide ions were generated from MS-TOF data. We applied Classification and Regression Tree analysis to build a decision algorithm, which achieved 77% correct classification rate across the three groups. A second cohort of 10 ATL, 10 HAM and 10 control samples was used to validate this result. Linear discriminate analysis was performed to verify and visualize class separation. Affinity and sizing chromatography coupled with tandem mass spectrometry was used to identify three peaks specifically overexpressed in ATL: an 11.7 kDa fragment of alpha trypsin inhibitor, and two contiguous fragments (19.9 and 11.9 kDa) of haproglobin-2. To the best of our knowledge, this is the first application of protein profiling to distinguish between two disease states resulting from a single infectious agent.

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
Figure 2
Figure 3
Figure 4
Figure 5
Figure 6
Figure 7

Similar content being viewed by others

References

  1. Hobbs SK, Shi G, Homer R, Harsh G, Atlas SW, Bednarski MD . Magnetic resonance image-guided proteomics of human glioblastoma multiforme. J Magn Reson Imaging 2003; 18: 530–536.

    Article  Google Scholar 

  2. Bangham CR . HTLV-1 infections. J Clin Pathol 2000; 53: 581–586.

    Article  CAS  Google Scholar 

  3. de The G, Bomford R . An HTLV-I vaccine: why, how, for whom? AIDS Res Hum Retroviruses 1993; 9: 381–386.

    Article  CAS  Google Scholar 

  4. Tajima K . The fourth nation-wide study of adult T-cell leukemia/lymphoma (ATL) in Japan: estimates of risk of ATL and its geographic and clinical features. Int J Cancer 1990; 45: 237–243.

    Article  CAS  Google Scholar 

  5. Pawson R, Richardson DS, Pagliuca A, Kelsey SM, Hoque S, Breuer J et al. Adult T-cell leukemia/lymphoma in London: clinical experience of 21 cases. Leuk Lymphoma 1998; 16: 32–50.

    Google Scholar 

  6. Matutes E, Chan LC . Mixed-lineage leukemia revisited: acute lymphocytic leukemia with myeloperoxidase-positive blasts by electron microscopy. Blood 1991; 77: 410–411.

    CAS  PubMed  Google Scholar 

  7. Group LS . Major prognostic factors of patients with adult T-cell leukemia–lymphoma: a cooperative study. Leuk Res 1991; 15: 81–90.

    Article  Google Scholar 

  8. Mora CA, Osame M, Jacobson S . Human T lymphotrophic virus type-I associated myelopathy/tropical spastic paraparesis (HAM/TSP): therapeutic approach. Curr Treat Options Infect Dis 2003; 5: 443–455.

    Google Scholar 

  9. Li J, Zhang Z, Rosenzweig J, Wang YY, Chan DW . Proteomics and bioinformatics approaches for identification of serum biomarkers to detect breast cancer. Clin Chem 2002; 48: 1296–1304.

    CAS  PubMed  Google Scholar 

  10. Adam BL, Qu Y, Davis JW, Ward MD, Clements MA, Cazares LH et al. Serum protein fingerprinting coupled with a pattern-matching algorithm distinguishes prostate cancer from benign prostate hyperplasia and healthy men. Cancer Res 2002; 62: 3609–3614.

    CAS  PubMed  Google Scholar 

  11. Wadsworth JT, Somers KD, Cazares LH, Malik G, Adam BL, Stack Jr BC et al. Serum protein profiles to identify head and neck cancer. Clin Cancer Res 2004; 10: 1625–1632.

    Article  CAS  Google Scholar 

  12. Vlahou A, Schellhammer PF, Mendrinos S, Patel K, Kondylis FI, Gong L et al. Development of a novel proteomic approach for the detection of transitional cell carcinoma of the bladder in urine. Am J Pathol 2001; 158: 1491–1501.

    Article  CAS  Google Scholar 

  13. Petricoin EF, Ardekani AM, Hitt BA, Levine PJ, Fusaro VA, Steinberg SM et al. Use of proteomic patterns in serum to identify ovarian cancer. Lancet 2002; 359: 572–577.

    Article  CAS  Google Scholar 

  14. Qu Y, Adam BL, Yasui Y, Ward MD, Cazares LH, Schellhammer PF et al. Boosted decision tree analysis of surface-enhanced laser desorption/ionization mass spectral serum profiles discriminates prostate cancer from noncancer patients. Clin Chem 2002; 48: 1835–1843.

    CAS  PubMed  Google Scholar 

  15. Bertone P, Kluger Y, Lan N, Zheng D, Christendat D, Yee A et al. SPINE: an integrated tracking database and data mining approach for identifying feasible targets in high-throughput structural proteomics. Nucleic Acids Res 2001; 29: 2884–2898.

    Article  CAS  Google Scholar 

  16. Kosuda S, Ichihara K, Watanabe M, Kobayashi H, Kusano S . Decision-tree sensitivity analysis for cost-effectiveness of whole-body FDG PET in the management of patients with non-small-cell lung carcinoma in Japan. Ann Nucl Med 2002; 16: 263–271.

    Article  Google Scholar 

  17. Semmes OJ, Feng Z, Adam BL, Banez LL, Bigbee WL, Campos D et al. Evaluation of serum protein profiling by surface-enhanced laser desorption/ionization time-of-flight mass spectrometry for the detection of prostate cancer: I. Assessment of platform reproducibility. Clin Chem 2005; 51: 102–112.

    Article  CAS  Google Scholar 

  18. Sun Z, Yang P . Role of imbalance between neutrophil elastase and alpha 1-antitrypsin in cancer development and progression. Lancet Oncol 2004; 5: 182–190.

    Article  CAS  Google Scholar 

  19. Arredouani M, Matthijs P, Van Hoeyveld E, Kasran A, Baumann H, Ceuppens JL et al. Haptoglobin directly affects T cells and suppresses T helper cell type 2 cytokine release. Immunology 2003; 108: 144–151.

    Article  CAS  Google Scholar 

  20. Langlois MR, Delanghe JR . Biological and clinical significance of haptoglobin polymorphism in humans. Clin Chem 1996; 42: 1589–1600.

    CAS  PubMed  Google Scholar 

  21. Turner GA . Haptoglobin A potential reporter molecule for glycosylation changes in disease. Adv Exp Med Biol 1995; 376: 231–238.

    Article  CAS  Google Scholar 

  22. Lee HB, Yoo OJ, Ham JS, Lee MH . Serum alpha 1-antitrypsin in patients with hepatocellular carcinoma. Clin Chim Acta 1992; 206: 225–230.

    Article  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Microbiology and Molecular Cell Biology, Eastern Virginia Medical School, Norfolk, VA, USA

    O J Semmes, L H Cazares, M D Ward, L Qi & M Moody

  2. Center for Biomedical Proteomics, Eastern Virginia Medical School, Norfolk, VA, USA

    O J Semmes, L H Cazares, M D Ward & L Qi

  3. Viral Epidemiology Branch, Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA

    E Maloney & M Hisada

  4. Metabolism Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA

    J Morris

  5. Department of Mathematics College of William & Mary, Williamsburg, VA, USA

    M W Trosset

  6. Proteomics Center, Harvard Medical School, Boston, MA, USA

    S Gygi

  7. Viral Immunology Section, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, MD, USA

    S Jacobson

Authors
  1. O J Semmes
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. L H Cazares
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. M D Ward
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. L Qi
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. M Moody
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. E Maloney
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. J Morris
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. M W Trosset
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. M Hisada
    View author publications

    You can also search for this author in PubMed Google Scholar

  10. S Gygi
    View author publications

    You can also search for this author in PubMed Google Scholar

  11. S Jacobson
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to O J Semmes.

Additional information

These studies were supported by a Translational Research Grant from the Leukemia and Lymphoma Society to OJS

Rights and permissions

Reprints and permissions

About this article

Cite this article

Semmes, O., Cazares, L., Ward, M. et al. Discrete serum protein signatures discriminate between human retrovirus-associated hematologic and neurologic disease. Leukemia 19, 1229–1238 (2005). https://doi.org/10.1038/sj.leu.2403781

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/sj.leu.2403781

Keywords

This article is cited by

Search

Advanced search

Quick links