Journal of Hematology & Thromboembolic Diseases

Journal of Hematology & Thromboembolic Diseases
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Short Communication - (2015) Volume 3, Issue 3

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Serum Soluble CD30 Levels to Detect Activation and Aggression Status of Adult T-Cell Leukemia/Lymphoma Cells

Shigeki Takemoto1,2*, Ratiorn Pornkuna2,3 and Chie Nishioka4
1Clinical Laboratory, National Hospital Organization Kumamoto Medical Center, Kumamoto, Japan
2Department of International Cooperation, Graduate School of Medical Sciences, Kumamoto University, Kumamoto, Japan
3Nursing Department, Khon Kaen Regional Hospital, Khon Kaen, Thailand
4Department of Hematology and Respiratory Medicine, Kochi Medical School, Kochi University of Technology, Nankoku, Kochi, Japan
*Corresponding Author: Shigeki Takemoto, M.D., Ph.D., Chief of Clinical laboratory, National Hospital Organization Kumamoto Medical Center, 1-5 Ninomaru, Kumamoto 860-0008, Japan, Tel: +81-(0)96-353-6501, Fax: +81-(0)96-325-2519 Email:

Abstract

Adult T-cell leukemia/lymphoma (ATL) is one of aggressive mature T-cell malignancies. CD30 is a cell membrane protein expressed on activated T-cell. While a limited number of ATL cells show the CD30 expression, high levels of soluble CD30 (sCD30) are detected in serum of ATL patients. It is known that a disintegrin and metalloproteinase (ADAM)10 and ADAM17 are ubiquitously expressed in peripheral leukocytes including T cells. They are sheddases of CD30 and IL-6 receptor (IL-6R) from cell surface as well as cleaving enzymes of E-cadherin and extracellular matrix. High levels of sIL-6R/IL-6 complex induce CRP production in the liver of ATL patients. Therefore the elevation of sCD30 and CRP levels indirectly indicated the activation status of ATL cells and the risk of invasion and tissue injury of important organs such as lung via metalloproteinases activation on ATL cells in vivo. Activated ATL cells may play a role for clinical aggression in ATL.

Keywords: Soluble CD30 (sCD30); Adult T-cell leukemia/ lymphoma (ATL); T-cell activation; A disintegrin and metalloproteinase

Short Communication

Adult T-cell leukemia/lymphoma (ATL) is one of aggressive mature T-cell malignancies [1]. We recently reported that levels of soluble CD30 (sCD30) were significant predictors of overall survival both before the initial therapy and before allogeneic hematopoietic stem cell transplantation (HSCT) at National Hospital Organization Kumamoto Medical Center [2].

Regarding HSCT, we found that the combination of sCD30 levels and CRP levels may be a powerful tool to predict the early death of patients undergoing HSCT. It is conceivable that elevated sCD30 levels and C-reactive protein (CRP) values are associated with an active state of residual ATL cells before the immunosuppressant therapy (Figure 1).

haematology-thromboembolic-peripheral-blood

Figure 1: Aggressive ATL cells in peripheral blood. Among activation markers, CD30 expression is induced by T cell activation. CD30 is shed following activation of a disintegrin and metalloproteinase (ADAM)10 and/or ADAM17 on the surface of ATL cells. Either ADAM10 and/or 17 cleave E-cadherin and extracellular matrix. Signal transducer and activator of transcription 3 is activated (yellow nucleus) and promoting proliferation and anti-apoptosis of ATL cells.

Conditioning therapy probably activates tissue macrophages, leading to further activation of residual ATL cells following cytokine storm.

CD30 is a cell membrane protein of the tumor necrosis factor receptor superfamily and is expressed on activated T-cell and B-cell, as well as on some tumor virus-infected T cells and B cells [3]. CD30 is constitutively expressed in some pathological conditions such as Hodgkin/Reed-Sternberg cells or anaplastic large lymphoma cells [4], while a part of the ATL cells isolated from patients is positive for CD30 expression on the cell surface [5-7].

Using 30% expression as a cut-off positive value, CD30 expression was predominantly seen in the acute type and lymphoma-type but not in the chronic type or smoldering type [6,7]. It is suggested that CD30 expression is induced on the surface of ATL cells as a progression of disease. In contrast, sCD30 levels were elevated in serum of ATL patients in spite of subtype of ATL but not in HTLV-1 carriers (Table 1).

Patient Subtype(pg/ml) IL-10(pg/ml) IL-4(pg/ml) IL-5(pg/ml) IL-6(pg/ml) IL-2(pg/ml) IFN-g(pg/ml) sCD30(U/ml) IgG(mg/dl) IgM(mg/dl) IgA(mg/dl)
1 Acute 34.6 14.4 16.9 10.8 64.1 10.7 540 1557 71 151
2 Acute 43.4 16.5 16.9 111.1 3 11.8 480 913 227 170
3 Acute 37.7 21.6 17.6 4.5 2.5 13.7 542.8 928 37 144
4 Acute 205.3 16.5 128.8 20.8 4.4 11.8 568.4 1850 57 228
5 Acute 1.3 17.6 16.8 0 12.7 10.9 513.2 ND* ND* ND*
6 Acute (replapse) 33 14.8 25.9 16 4.9 11.8 626.8 ND* ND* ND*
7 Lymphoma 6.2 16.1 16.8 26 92.6 11.8 300.1 ND* ND* ND*
8 Lymphoma (relapse) 5.2 0 102.3 35.4 0 12.1 541.2 1210 77 385
9 Lymphoma 8.3 9.8 3.4 8.6 11.4 7.5 141.6 1430 64 264
10 Chronic 5.4 0 3.3 8.7 11 7.3 255.8 668 45 106
11 Carrier 6.2 1 3.3 26.1 11.9 12.2 39.9 ND* ND* ND*
  Healthy donor (n=5) 3.0 ± 2.4▪ 0.4 ± 0.6▪ 4.0 ± 0.6▪ 0.7 ± 1.5▪ 7.4 ± 4.7▪ 4.4 ± 3.6▪ 40.1 ± 9.0▪ 920-1800♦ 60-285♦ 110-450♦

Table 1: Serum levels of Cytokines and Proteins, ▪Average ± SD ♦the normal changes *no data.

The CRP level is controlled by circulating IL-6 levels, which are elevated in ATL patients [8,9]. Actually, IL-6 levels were elevated even in the serum of HTLV-1 carriers (Table 1). Furthermore, soluble IL-6 receptor (sIL-6R) is produced by ATL cells and sIL-6R/IL-6 complex works as the agonist of IL-6R signaling [10,11]. This may be the reason why signal transducer and activator of transcription 3 is constitutively activated in ATL cells in vivo [12].

It is known that a disintegrin and metalloproteinase (ADAM)10 and ADAM17 are ubiquitously expressed in peripheral leukocytes including T cells. They are sheddases of CD30 and IL-6R from cell surface as well as cleaving enzymes of E-cadherin and extracellular matrix [13-17]. It is speculated that the expression and shedding of CD30 is induced in only activated ATL cells [18]. High levels of sIL-6R/IL-6 complex induce CRP production in the liver of ATL patients. Therefore the elevation of sCD30 and CRP levels indirectly indicated the activation status of ATL cells and the risk of invasion and tissue injury of important organs such as lung via metalloproteinases activation on ATL cells in vivo (Figure 1) [2]. Activated ATL cells may play a role for clinical aggression in ATL.

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Citation: Takemoto S, Pornkuna R, Nishioka C (2015) Serum Soluble CD30 Levels to Detect Activation and Aggression Status of Adult T-Cell Leukemia/Lymphoma Cells. J Hematol Thrombo Dis 3:205.

Copyright: © 2015 Takemoto S, et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution and reproduction in any medium, provided the original author and source are credited.
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