ACLS
HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
QUICK SEARCH:   [advanced]


     

This Article
Right arrow Abstract Freely available
Right arrow Full Text (PDF)
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Right arrow Citation Map
Services
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrow reprints & permissions
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Moon, Y.
Right arrow Articles by Han, K.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Moon, Y.
Right arrow Articles by Han, K.
Annals of Clinical & Laboratory Science 34:410-415 (2004)
© 2004 Association of Clinical Scientists

Plasma Soluble Interleukin-2 Receptor (sIL-2R) Levels in Patients with Acute Leukemia

Yeonsook Moon2, Yonggoo Kim1, Myungshin Kim1, Jihyang Lim1, Chang Suk Kang1, Won Il Kim1, Sang In Shim1, Nak Gyun Chung3, Yoon Hee Park4, Woo Sung Min4 and Kyungja Han1
1 Department of Clinical Pathology, Catholic University Medical College, Seoul; 2 Department of Laboratory Medicine, Inha University Medical College, Incheon; 3 Department of Pediatrics and 4 Department of Internal Medicine, Catholic University Medical College, Seoul, Korea

Address correspondence to Kyungja Han, M.D.; #62, Youido-dong, Youngdeungpo-gu, St. Mary’s Hospital; Department of Clinical Pathology, College of Medicine, The Catholic University of Korea, Seoul, Korea 150-713; tel 82 2 3779 1310; fax 82 2 783 6648; e-mail: hankja{at}catholic.ac.kr.


   Abstract
Top
 Abstract
Introduction
 Materials and Methods
 Results
 Discussion
 References
 
The plasma soluble interleukin-2 receptor (sIL-2R) level was higher in 137 patients with acute leukemia (1,489 ± 1,798U/ml, including 98 cases of acute myeloid leukemia (AML), 1,063 ± 1,414 U/ml, and 39 cases of acute lymphoblastic leukemia (ALL), 2,561 ± 2,194 U/ml), compared to 49 normal control subjects, 421±151 U/ml). The ALL patients showed elevated plasma sIL-2R levels more frequently than the AML patients (92.3% vs 44.9%). No patient with either hypoplastic AML or AML with multilineage dysplasia and only 1 of 13 patients with acute promyelocytic leukemia (APL) had an elevated plasma sIL-2R level. All the My+ ALL patients (15 cases) showed elevated plasma sIL-2R levels. Plasma sIL-2R levels were significantly lower after chemotherapy in the ALL patients, but were not significantly lower in the AML patients. IL-2R was expressed on the leukemic cells in 36 (53.7%) of 67 AML and in 9 (21.4%) of 42 ALL cases. None of the AML M3, M4, M5, M6, or M7 subgroups showed IL-2R expression. The My+ ALL patients (42.9%, 6/14) showed IL-2R expression more frequently than the other ALL subgroups (10.7%, 3/28) (p = 0.025). The plasma sIL-2R level was correlated with the proportion of leukemic cells expressing IL-2R in acute leukemia. However, there were many cases, particularly ALL cases, who had elevated plasma sIL-2R levels without IL-2R expression on their leukemic cells. These results suggest that the plasma sIL-2R level is a valuable marker for monitoring ALL after chemotherapy, particularly in My+ ALL cases, and that the T cell immune reaction to leukemia appears to be much higher in ALL patients than in AML patients.

(received 4 September 2004; accepted 15 September 2004)

Keywords: soluble interleukin-2 receptor (sIL-2R), acute myelocytic leukemia (AML), acute lymphoblastic leukemia (ALL)


   Introduction
Top
 Abstract
 Introduction
Materials and Methods
 Results
 Discussion
 References
 
The soluble interleukin-2 receptor (sIL-2R) is released along with interleukin-2 from activated T cells. The level of sIL-2R in serum or plasma reflects the immune activity and is an important marker of leukemogenesis of adult T-cell leukemia/lymphoma (ATL) [1]. The serum level of sIL-2R is markedly increased in malignant lymphoma [2–5], and is also increased in other diseases, eg, hairy cell leukemia, carcinoma, autoimmune disorders, and infectious disorders [6–11]. Serum sIL-2R level is suitable for monitoring disease activity since it has relatively low inter-individual and intra-individual variation [12].

In acute lymphoblastic leukemia (ALL), the levels of sIL-2R in serum are significantly higher than in normal people. In addition, the level is higher in patients with a poorer outcome, and decreases after induction chemotherapy [13–14]. The level of sIL-2R in serum is also significantly higher in acute myeloid leukemia (AML) patients [15,16], and a few studies have shown that their serum sIL-2R level decreases after chemotherapy [17,18].

IL-2R expression has been observed on certain ALL and AML leukemic cells [19,20], in blastic crisis of chronic myelocytic leukemia (CML-BC) [21], hairy cell leukemia (HCL) [22], Burkitt’s lymphoma [23], and ATL associated with human T cell leukemia viral (HTLV-1) infection [24]. However, the significance of sIL-2R levels in various types of acute leukemia and the relationship between the proportion of IL-2R expression on leukemic cells and the sIL-2R level in serum or plasma have not been examined.

This study measured the plasma sIL-2R level in patients with acute leukemia prior to any treatment and at remission, and examined the significance of the plasma sIL-2R level as a response marker for acute leukemia. In this study, a relationship between IL-2R expression on leukemic cells and the plasma sIL-2R level in acute leukemia was demonstrated. In addition, IL-2R expression of T lymphocytes in the bone marrow was measured in order to determine the origin of the plasma sIL-2R.


   Materials and Methods
Top
 Abstract
 Introduction
 Materials and Methods
Results
 Discussion
 References
 
Patients.  All patients provided informed consent to participate in this study.

Plasma sIL-2R levels were measured in 137 patients with acute leukemia (98 AML cases and 39 ALL cases) at the time of initial diagnosis. The patients’ ages ranged from 4 mo to 82 yr (median age 36 yr). Plasma sIL-2R levels were measured in 21 of these patients with acute leukemia at the time of the initial diagnosis and during remission after chemotherapy. In addition, plasma sIL-2R levels were measured in 46 healthy persons (20 children, 26 adults).

The IL-2R expression level was measured on leukemic cells from 109 patients with acute leukemia (67 AML cases and 42 ALL cases) and on bone marrow cells from 20 healthy donors. The plasma sIL-2R levels and IL-2R expression on the leukemic cells in 74 of these acute leukemia cases were determined.

Blood samples from the patients and healthy persons were anticoagulated with EDTA and the plasma samples were divided into aliquots and stored at –75°C for sIL-2R analysis.

Measurements of soluble interleukin-2 receptors.  The plasma sIL-2R levels were determined using a sandwich enzyme immunoassay method (CELL-FREE IL-2R Medex, Kyowa Medex Co, Tokyo, Japan). All specimens were assayed in duplicate. Briefly, the sIL-2R molecules available in the patient samples or the standard controls were bound to polystyrene microtiter wells that were previously coated with anti-IL-2R monoclonal antibodies. Horseradish-peroxidase-conjugated anti-IL-2R bound to the IL-2R antigen was captured by the first antibody, which completed the sandwich. After washing the vessels to remove the unbound enzyme-conjugated mAb, a substrate was added to the wells. The reaction was then quenched by the addition of a H2SO4 solution and the absorbance was determined at 490 nm. Standard curves were prepared using different reference preparations containing known sIL-2R concentrations. The patients with plasma sIL-2R levels that exceeded 723 U/ml (ie, the mean + 2 SD of healthy controls) were considered to have elevated plasma sIL-2R levels.

Detection of IL-2R on leukemic cells and normal lymphocytes.  All of the monoclonal antibodies were purchased from Becton-Dickinson Bioscience (San Jose, CA). Fluorescein isothiocyanate-labeled anti-CD3 and phycoerythrin-labeled anti-IL-2R (CD25) were used. All the leukemic samples were stained both with FITC- and PE-labeled mAb directed against CD3, CD5, CD7, CD10, CD13, CD14, CD19, CD33, CD34, CD41, anti-{kappa}, anti-{lambda}, and HLA-DR and with negative isotypic control antibodies. Two-color immunostaining was performed in order to determine if CD3 and/or CD25 was expressed on the same cells in the bone marrow from the acute leukemia patients and the healthy donors.

The erythrocytes were then lysed by incubation in a lysis solution (Becton-Dickinson Bioscience). After washing with phosphate-buffered saline (PBS), 20,000 cells were analyzed by flow cytometry (FACS Calibur, Becton-Dickinson System) using the CellQuest program. The lymphocytes or blast cell population were gated by dot plots showing the forward (FSC) and side scatter (SSC) properties of the cells. The cut-off line was set to the fluorescent intensity, which was 2 % of the cells stained with negative isotypic control antibody. The cells showing fluorescence intensities above this cut-off were considered to be positive cells. The samples were considered to be positive for the CD3 surface antigens if >20% of the leukemic cells showed intensities above the control. If >10% of leukemic cells showed intensities above the control, the samples were considered positive for the CD25 and CD41 surface antigens.

Statistical analysis.  The plasma sIL-2R levels were expressed as mean ± SD. Statistical comparisons between the patients and the control group, and between the patients with active disease and those in CR, were performed by the Mann-Whitney U test and the paired-sample T test using the SPSS program. Correlations between the sIL-2R levels in each patient group and IL-2R expression on the leukemic cells were tested by Pearson’s correlation coefficient using the SPSS program. Comparisons between each subgroup were analyzed by an ANOVA test using the SPSS program. A p value <0.05 was considered significant.


   Results
Top
 Abstract
 Introduction
 Materials and Methods
 Results
Discussion
 References
 
Plasma sIL-2R levels.  The plasma sIL-2R level in the 137 patients with acute leukemia averaged 1,489 ± 1,798 U/ml. In the 98 patients with AML, the level was 1,063 ± 1,414 U/ml and that in the 39 patients with ALL was 2,561 ± 2,194 U/ml. All of these levels were higher than sIL-2R level in the normal controls (421 ± 151 U/ml) (Table 1Go).


View this table:
[in this window]
[in a new window]
  		Table 1. Plasma sIL-2R levels in acute leukemia.
 
Forty-four (44.9%) of the 98 patients with AML had an elevated plasma sIL-2R level. Thirty-six (92.3%) of the 39 patients with ALL had an elevated plasma sIL-2R (Table 2Go). The plasma sIL-2R level was different in the subgroups of acute leukemia. In AML, none of the patients with hypoplastic AML (5 cases) and AML with multilineage dysplasia (6 cases) had an elevated plasma sIL-2R level. Only 1 of the 13 patients with APL had an elevated plasma sIL-2R level. There were no significant differences in plasma sIL-2R levels among the FAB subgroups of AML except for APL (p = <0.0001). All of the 15 ALL patients with myeloid antigen positive ALL (My+ ALL) had elevated plasma sIL-2R levels, and the plasma sIL-2R level of these patients (3,521 ± 151 U/ml) was higher than in the other ALL subgroups (1,997 ± 1,751 U/mL, p = 0.03) (Table 3Go).


View this table:
[in this window]
[in a new window]
  		Table 2. Proportion of elevated plasma sIL-2R results in patients with acute leukemia (elevated value = >723 U/ml).
 

View this table:
[in this window]
[in a new window]
  		Table 3. Proportions of elevated plasma sIL-2R results in patients with acute leukemia, according to FAB subgroups (elevated value = 723 U/ml).
 
The plasma sIL-2R levels in ALL patients were significantly lower following chemotherapy (12 cases, p = 0.02); the decrease was not significant in the AML patients following chemotherapy (9 cases, p=0.09) (Table 4Go).


View this table:
[in this window]
[in a new window]
  		Table 4. Results of plasma sIL-2R assays in patients with acute leukemia before and after chemotherapy.
 
IL-2R expression of leukemic cells and T lymphocytes in bone marrow.  IL-2R was expressed on the surface of the leukemic cells in 36 (53.7%) of the 67 AML cases and in 9 (21.4%) of the 42 ALL cases. IL-2R was not expressed on the surface of the leukemic cells in 15 cases of the AML M3, M4, M5, M6, or M7 subgroups.

The My+ ALL cases (42.9%, 6/14) showed IL-2R expression more frequently than the other ALL cases (10.7%, 3/28) (p = 0.03) (Table 5Go). The proportions of IL-2R expressed in bone marrow T lymphocytes were similar to normal controls (p >0.05); AML 11.2 ± 11.3%, ALL 10.8 ± 11.4%, normal controls 9.29 ± 6.41%.


View this table:
[in this window]
[in a new window]
  		Table 5. Expression of IL-2R on leukemic cells, based on flow cytometric analysis.
 
Correlation of plasma sIL-2R levels and IL-2R expression.  Significant correlations were found between the plasma sIL-2R level and the proportion of leukemic cells expressing IL-2R in the AML patients (r = 0.698, p = <0.001) and in ALL cases (r = 0.704, p <0.001).


   Discussion
Top
 Abstract
 Introduction
 Materials and Methods
 Results
 Discussion
References
 
Plasma IL-2R levels were significantly higher in the ALL and AML patients than in the normal controls (p<0.05). In particular, the plasma sIL-2R level in the ALL patients was higher (2,561 ± 2,194 U/ml) than the normal controls (421 ± 151 U/ml), and most (92.3%) had elevated plasma IL-2R levels.

The plasma IL-2R levels differed according to acute leukemia subgroups. Interestingly, the plasma IL-2R levels were not higher in any of hypoplastic AML and AML with multilineage dysplasia patients or in most of APL patients. It has been reported that the serum sIL-2R level was lower in APL patients than in those with acute myelomonocytic leukemia or acute monocytic leukemia [16]. There is no report regarding the plasma sIL-2R level in hypoplastic AML or AML patients with multilineage dysplasia.

In the ALL patients, the plasma sIL-2R level was elevated in all patients with My+ ALL. This suggests that the myeloid antigen on the leukemic cells in ALL patients plays a role in T cell activation. These variations according to the acute leukemia subgroups might be due to differences in the immune response in these diseases and/or IL-2R expression of the leukemic cells. Although the physiological and pathological function of sIL-2R is not well defined, it can bind interleukin 2 (IL-2) and might downregulate the host immune response by competing with the normal lymphocyte cellular IL-2R. Therefore, the increased levels of sIL-2R have been suggested to enhance neoplastic growth by suppressing the host antitumor immunity in patients with a malignancy [26,27].

Higher levels of serum IL-2R have been reported to be associated with more advanced disease, greater tumor burden, and poorer outcome [13,28,29]. The present study found that plasma IL-2R levels in patients in complete remission were significantly lower than the initial level in acute leukemia patients. This suggests that the plasma sIL-2R level is related to the tumor burden and could be a valuable marker for monitoring acute leukemia after chemotherapy.

Pui et al [15] reported IL-2R expression on the leukemic cells in 1 of 33 children with AML. In the present study, IL-2R was expressed on leukemic cells in 53.7% of AML cases and in 21.4% of ALL cases. The plasma sIL-2R levels were related to the IL-2R expression level on the leukemic cells (p <0.05).

There were many cases, particularly ALL patients, who had elevated plasma sIL-2R levels without IL-2R expression on their leukemic cells. This suggests that the plasma sIL-2R originates from other cells (possibly activated T lymphocytes) but not from leukemic cells. Therefore, the T cell immune reaction to leukemia appears to be much higher in ALL than in AML.

Interestingly, IL-2R was not expressed on the leukemic cells in the AML M3, M4, M5, M6, or M7 subgroups. The My+ ALL cases showed IL-2R expression more frequently than the other ALL. A previous report also showed a correlation between IL-2R expression and the co-expression of the different lineage markers [25].

In conclusion, the plasma sIL-2R level was higher in acute leukemia patients than in the normal controls, and it differed according to the acute leukemia subgroups. sIL-2R might be a valuable marker for monitoring ALL after chemotherapy, particularly in patients with My+ ALL. The T cell immune reaction to leukemia appears to be much higher in ALL patients than in AML patients.


View this table:
[in this window]
[in a new window]
  		Table 6. Correlation between plasma sIL-2R level and proportion of IL-2R+ cells.
 

   References
Top
 Abstract
 Introduction
 Materials and Methods
 Results
 Discussion
 References
 
  1. Kamihira S, Atogami S, Sohda H, Momita S, Yamada Y, Tomonaga M. Significance of soluble interleukin-2 receptor levels for evaluation of the progression of adult T-cell leukemia. Cancer 1994;73:2753–2758.[Medline]
  2. Motokura T, Kobayashi Y, Fujita A, Nakamura Y, Taniguchi T, Uchimaru K, Asano S. Clinical significance of serial measurement of the serum levels of soluble interleukin-2 receptor and soluble CD8 in malignant lymphoma. Leuk Lymphoma 1995;16:355–362.[Medline]
  3. Kalmanti M, Karamolengou K, Dimitriou H, Tosca A, Vlachonikolis I, Peraki M, Georgoulias V, Kalmantis T. Serum levels of tumor necrosis factor and soluble interleukin 2 receptor as markers of disease activity and prognosis in childhood leukemia and lymphoma. Int J Hematol 1993;57:147–152.[Medline]
  4. Niitsu N, Iijima K, Chizuka A. A high serum-soluble interleukin-2 receptor level is associated with a poor outcome of aggressive non-Hodgkin’s lymphoma. Eur J Haematol 2001;66:24–30.[Medline]
  5. Ohno H, Ishikawa T, Kitajima H, Nomura S, Suzuki T, Konishi H, Ohno Y, Onishi R, Konaka Y, Arima N, Doi S, Nasu K, Takahashi T, Tsudo M, Fukuhara S, Uchiyama T. [Significance of soluble interleukin-2 receptor alpha chain in the management of patients with malignant lymphoma: a multi-center study]. Rinsho Ketsueki 2002; 43:170–175.[Medline]
  6. Lauria F, Raspadori D, Benfenati D, Rondelli D, Pallotti A, Tura S. Biological markers and minimal residual disease in hairy cell leukemia. Leukemia 1992;6(Suppl 4):149–151.
  7. 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; 7:312–317.[Medline]
  8. Sedlaczek P, Frydecka I, Gabrys M, Van Dalen A, Einarsson R, Harlozinska A. Comparative analysis of CA125, tissue polypeptide specific antigen, and soluble interleukin-2 receptor alpha levels in sera, cyst, and ascitic fluids from patients with ovarian carcinoma. Cancer 2002; 95:1886–1893.[Medline]
  9. Dejica D. Serum soluble IL-2 receptor as a marker of lymphocyte activation in some autoimmune diseases. Effect of immunosuppressive therapy. Roum Arch Microbiol Immunol 2001;60:183–201.[Medline]
  10. Choi JH, Suh CH, Lee YM, Suh YJ, Lee SK, Kim SS, Nahm DH, Park HS. Serum cytokine profiles in patients with adult onset Still’s disease. J Rheumatol 2003;30: 2422–2427.[Abstract/Free Full Text]
  11. Tanaka H, Narita M, Teramoto S, Saikai T, Oashi K, Igarashi T, Abe S. Role of interleukin-18 and T-helper type 1 cytokines in the development of Mycoplasma pneumoniae pneumonia in adults. Chest 2002;121:1493–1497.[Abstract/Free Full Text]
  12. Cava F, Gonzalez C, Pascual MJ, Navajo JA, Gonzalez-Buitrago JM. Biological variation of interleukin 6 (IL-6) and soluble interleukin 2 receptor (sIL2R) in serum of healthy individuals. Cytokine 2000;12:1423–1425.[Medline]
  13. Pui CH, Ip SH, Iflah S, Behm FG, Grose BH, Dodge RK, Crist WM, Furman WL, Murphy SB, Rivera GK. Serum interleukin 2 receptor levels in childhood acute lymphoblastic leukemia. Blood 1988;71:1135–1137.[Abstract/Free Full Text]
  14. Cetingul N, Yener E, Oztop S, Nisli G. Serum soluble interleukin-2 receptors and tumor necrosis factor-alpha in hematological malignancies of childhood. Acta Paediatr Jpn 1994;36:49–52.[Medline]
  15. Pui CH, Schell MJ, Vodian MA, Kline S, Mirro J, Crist WM, Behm FG. Serum CD4, CD8, and interleukin-2 receptor levels in childhood acute myeloid leukemia. Leukemia 1991;5:249–254.[Medline]
  16. Cimino G, Amadori S, Cava MC, De Sanctis V, Petti MC, Di Gregorio AO, Sgadari C, Vegna L, Cimino G, Mandelli F. Serum interleukin-2 (IL-2), soluble IL-2 receptors and tumor necrosis factor-alfa levels are significantly increased in acute myeloid leukemia patients. Leukemia 1991;5:32–35.
  17. Iizuka Y, Aiso M, Ohshima T, Sawada S, Horie T. Serum soluble CD4, CD8 and IL-2R levels in adult acute myeloid leukemia in remission. Med Oncol Tumor Pharmacother 1992;9:57–64.[Medline]
  18. Lim SH, Worman CP, Goldstone AH. Lymphocyte activation in patients with acute myeloid leukaemia. Evidence for the presence of myeloblast antigen? Cancer Immunol Immunother 1991;33:417–420.[Medline]
  19. Armitage RJ, Lai AP, Roberts PJ, Cawley JC. Certain myeloid cells possess receptors for interleukin-2. Br J Haematol 1986;64:799–807.[Medline]
  20. Erber WN, Mason DY. Expression of the interleukin-2 receptor (Tac antigen/CD25) in hematologic neoplasms. Am J Clin Pathol 1988;89:645–648.[Medline]
  21. Motoi T, Uchiyama T, Hori T, Itoh K, Uchino H, Ueda R. Elevated serum-soluble interleukin-2 receptor (Tac antigen) levels in chronic myelogenous leukemia patients with blastic crisis. Blood 1989;74:1052–1057.[Abstract/Free Full Text]
  22. Korsmeyer SJ, Greene WC, Cossman J, Hsu SM, Jensen JP, Neckers LM, Marshall SL, Bakhashi A, Depper JM, Leonard WJ, Jaffe E, Waldmann TA. Rearrangement and expression of immunoglobulin genes and expression of Tac antigen in hairy cell leukemia. PNAS USA 1983;80: 4522–4526.[Abstract/Free Full Text]
  23. Waldmann TA, Goldman CK, Robb RJ, Depper JM, Leonard WJ, Sharrow SO, Bongiovanni KF, Korsmeyer SJ, Greene WC. Expression of interleukin 2 receptors on activated human B cells. J Exp Med 1984;160:1450–1466.[Abstract/Free Full Text]
  24. Depper JM, Leonard WJ, Kronke M, Waldmann TA, Greene WC. Augmented T cell growth factor receptor expression in HTLV-1-infected human leukemic T cells. J Immunol 1984;133:1691–1695.[Free Full Text]
  25. Nakase K, Kita K, Otsuji A, Anazawa H, Hoshino K, Sekine T, Shirakawa S, Tanaka I, Nasu K, Tsutani H, Dohy H, Tsudo M. Diagnostic and clinical importance of interleukin-2 receptor alpha chain expression on non-T-cell acute leukaemia cells. Br J Haematol 1992;80:317–326.[Medline]
  26. Rubin LA, Kurman CC, Fritz ME, Biddison WE, Boutin B, Yarchoan R, Nelson DL. Soluble interleukin 2 receptors are released from activated human lymphoid cells in vitro. J Immunol 1985;135:3172–3177.[Abstract]
  27. Greene WC, Leonard WJ, Depper JM, Nelson DL, Waldmann TA. The human interleukin-2 receptor: Normal and abnormal expression in T cells and in leukemias induced by the human T-lymphotropic retroviruses. Ann Intern Med 1986;105:560–572.
  28. Pui CH, Ip SH, Kung P, Dodge RK, Berard CW, Crist WM, Murphy SB. High serum ininterleukin-2 receptor levels are related to advanced disease and a poor outcome in childhood non-Hodgkin’s lymphoma. Blood 1987;70: 624–628.[Abstract/Free Full Text]
  29. Wagner DK, Kiwanuka J, Edwards BK, Rubin LA, Nelson DL, Magrath IT. Soluble interleukin-2 receptor levels in patients with undifferentiated and lymphoblastic lymphomas: correlation with survival. J Clin Oncol 1987;5: 1262–1274.[Abstract/Free Full Text]



This article has been cited by other articles:


Home page
 Ann Clin Lab SciHome page
W. Lee, S. J. Kim, S. Lee, J. Kim, M. Kim, J. Lim, Y. Kim, B. Cho, E. J. Lee, and K. Han
Significance of Cerebrospinal Fluid sIL-2R Level as a Marker of CNS Involvement in Acute Lymphoblastic Leukemia
Ann. Clin. Lab. Sci., October 1, 2005; 35(4): 407 - 412.
[Abstract] [Full Text] [PDF]

This Article
Right arrow Abstract Freely available
Right arrow Full Text (PDF)
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Right arrow Citation Map
Services
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrow reprints & permissions
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Moon, Y.
Right arrow Articles by Han, K.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Moon, Y.
Right arrow Articles by Han, K.

HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS