Annals of Laboratory Medicine

Korean Society for Laboratory Medicine (대한진단검사의학회)
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Clinical Relevance of Elevated Levels of Serum Soluble Interleukin-2 Receptor alpha (sIL-$2R{\alpha}$) in Patients with Non-Hodgkin's Lymphoma

  • Jo, Seon-A (Department of Laboratory Medicine, Pusan National University School of Medicine) ;
  • Hwang, Sang-Hyun (Department of Laboratory Medicine, Pusan National University School of Medicine) ;
  • Chang, Chul-Hun L. (Department of Laboratory Medicine, Pusan National University School of Medicine) ;
  • Kim, Shine-Young (Department of Laboratory Medicine, Pusan National University School of Medicine) ;
  • Shin, Ho-Jin (Department of Internal Medicine, Pusan National University School of Medicine) ;
  • Chung, Joo-Seop (Department of Internal Medicine, Pusan National University School of Medicine) ;
  • Sol, Mee-Young (Department of Pathology, Pusan National University School of Medicine) ;
  • Lee, Eun-Yup (Department of Laboratory Medicine, Pusan National University School of Medicine)
  • Received : 2010.04.26
  • Accepted : 2010.10.14
  • Published : 2010.12.01
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Abstract

Levels of soluble interleukin-2 receptor alpha (sIL-$2R{\alpha}$) are known to increase in the sera of patients with certain malignancies, including malignant lymphoma. This study aimed to assess the clinical significance of the sIL-$2R{\alpha}$ level in non-Hodgkin's lymphoma (NHL). We used ELISA to measure the sIL-$2R{\alpha}$ levels in 48 newly diagnosed and untreated patients with NHL and evaluated the correlation between the sIL-$2R{\alpha}$ levels and clinical characteristics and the International Prognostic Index (IPI). We monitored serum sIL-$2R{\alpha}$ in 7 patients to compare the changes in their clinical progress with these levels. High levels of serum sIL-$2R{\alpha}$ (${\geq}$2,000 U/mL) correlated well with parameters defining the high risk group according to the IPI, i.e., high tumor burden at diagnosis (stage III+IV) and lactate dehydrogenase ${\geq}$472 U/L. The levels were also associated with B symptoms, bone marrow involvement, and poor response to therapy. The sIL-$2R{\alpha}$ level decreased during complete remission and was elevated during disease progression or relapse. A high level of sIL-$2R{\alpha}$ was significantly associated with a low survival rate. These results suggest that serum sIL-$2R{\alpha}$ might be useful as a biomarker for evaluating the prognosis of patients with NHL at the time of diagnosis and during therapy. A well-controlled, large-scale study is needed to clarify the clinical significance of sIL-$2R{\alpha}$ in specific groups of NHL.

Keywords

Acknowledgement

Supported by : Pusan National University

References

  1. Armitage JO and Weisenburger DD. New approach to classifying non-Hodgkin's lymphomas: clinical features of the major histologic subtypes. Non-Hodgkin's Lymphoma Classification Project. J Clin Oncol 1998;16:2780-95.
  2. Setoyama Y, Imai J, Ishikawa T, Sakaida H, Takaori-Kondo A, Kawamata S, et al. Usefulness of the measurement of serum soluble IL-2 receptor alpha chain levels in clinical monitoring of non-Hodgkin lymphoma. Rinsho Byori 1994;42:834-42.
  3. A predictive model for aggressive non-Hodgkin's lymphoma. The International Non-Hodgkin's Lymphoma Prognostic Factors Project. N Engl J Med 1993;329:987-94. https://doi.org/10.1056/NEJM199309303291402
  4. Bien E and Balcerska A. Serum soluble interleukin 2 receptor alpha in human cancer of adults and children: a review. Biomarkers 2008;13:1-26. https://doi.org/10.1080/13547500701674063
  5. Gandhi MK, Lambley E, Burrows J, Dua U, Elliott S, Shaw PJ, et al. Plasma Epstein-Barr virus (EBV) DNA is a biomarker for EBV-positive Hodgkin's lymphoma. Clinical Cancer Research 2006;12:460-4. https://doi.org/10.1158/1078-0432.CCR-05-2008
  6. Rubin LA, Galli F, Greene WC, Nelson DL, Jay G. The molecular basis for the generation of the human soluble interleukin 2 receptor. Cytokine 1990;2:330-6. https://doi.org/10.1016/1043-4666(90)90062-X
  7. Waldmann TA. Anti-Tac (daclizumab, Zenapax) in the treatment of leukemia, autoimmune diseases, and in the prevention of allograft rejection: a 25-year personal odyssey. J Clin Immunol 2007;27:1-18. https://doi.org/10.1007/s10875-006-9060-0
  8. Kitagawa JI, Hara T, Tsurumi H, Goto N, Kanemura N, Yoshikawa T, et al. Serum-soluble interleukin-2 receptor (sIL-2R) is an extremely strong prognostic factor for patients with peripheral T-cell lymphoma, unspecified (PTCL- U). J Cancer Res Clin Oncol 2009;135:53-59. https://doi.org/10.1007/s00432-008-0440-0
  9. Oki Y, Kato H, Matsuo K, Kuwatsuka Y, Taji H, Yamamoto K, et al. Prognostic value of serum soluble interleukin-2 receptor level in patients with diffuse large B cell lymphoma, treated with CHOP- or RCHOP-based therapy. Leuk Lymphoma 2008;49:1345-51. https://doi.org/10.1080/10428190802108888
  10. Wakao D, Murohashi I, Tominaga K, Yoshida K, Kishimoto K, Yagasaki F, et al. Serum thymidine kinase and soluble interleukin-2 receptor predict recurrence of malignant lymphoma. Ann Hematol 2002;81:140-6. https://doi.org/10.1007/s00277-001-0421-8
  11. Goto H, Tsurumi H, Takemura M, Ino-Shimomura Y, Kasahara S, Sawada M, et al. Serum-soluble interleukin-2 receptor (sIL-2R) level determines clinical outcome in patients with aggressive non-Hodgkin's lymphoma: in combination with the International Prognostic Index. J Cancer Res Clin Oncol 2005;131:73-9. https://doi.org/10.1007/s00432-004-0600-9
  12. Janik JE, Morris JC, Pittaluga S, McDonald K, Raffeld M, Jaffe ES, et al. Elevated serum-soluble interleukin-2 receptor levels in patients with anaplastic large cell lymphoma. Blood 2004;104:3355-7. https://doi.org/10.1182/blood-2003-11-3922
  13. Yoshida S and Morii K. Serum concentrations of soluble interleukin-2 receptor in patients with malignant brain tumors. J Surg Oncol 2000;75:131-5. https://doi.org/10.1002/1096-9098(200010)75:2<131::AID-JSO10>3.0.CO;2-L
  14. Kaminska J, Kowalska M, Kotowicz B, Fuksiewicz M, Glogowski M, Wojcik E, et al. Pretreatment serum levels of cytokines and cytokine receptors in patients with non-small cell lung cancer, and correlations with clinicopathological features and prognosis. M-CSF - an independent prognostic factor. Oncology 2006;70:115-25. https://doi.org/10.1159/000093002
  15. Witkowska AM. On the role of sIL-2R measurements in rheumatoid arthritis and cancers. Mediators Inflamm 2005;2005:121-130. https://doi.org/10.1155/MI.2005.121
  16. Sakata H, Murakami S, Hirayama R. Serum soluble interleukin-2 receptor (IL-2R) and immunohistochemical staining of IL-2R/Tac antigen in colorectal cancer. Int J Clin Oncol 2002;7:312-7.
  17. Huang A, Quinn H, Glover C, Henderson DC, Allen-Mersh TG. The presence of interleukin-2 receptor alpha in the serum of colorectal cancer patients is unlikely to result only from T cell up-regulation. Cancer Immunol Immunother 2002;51:53-7. https://doi.org/10.1007/s00262-001-0250-6

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