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Annals of Clinical & Laboratory Science 36:7-15 (2006)
© 2006 Association of Clinical Scientists

Intracellular IL-4, IL-10, and IFN-{gamma} Levels of Leukemic Cells and Bone Marrow T Cells in Acute Leukemia

Hun Hee Park1, Myungshin Kim2, Bong-Hee Lee1, Jihyang Lim2, Yonggoo Kim, Eun Jung Lee2, Woo Sung Min3, Chang Suk Kang2, Won Il Kim2, Sang In Shim2 and Kyungja Han2
1 School of Life Science and Biotechnology, Korea University; 2 Department of Clinical Pathology and 3 Department of Internal Medicine, College of Medicine, Catholic University of Korea, Seoul, Korea

Address correspondence to Kyungja Han, M.D., Department of Clinical Pathology, Catholic University Medical College, St. Mary’s Hospital, Youngdeungpogu, Youido-dong 62, Seoul, Korea (South) 150-713; tel 82 2 3779-1297; fax 82 2 783 6648; e-mail hankja{at}catholic.ac.kr.


   Abstract
Top
 Abstract
Introduction
 Materials and Methods
 Results
 Discussion
 Acknowledgement
 References
 
The quantitative levels of intracellular cytokines IL-4, IL-10, and IFN-{gamma} (ie, the number of bound PE-conjugated antibody molecules/cell) of leukemic cells and bone marrow T cells (bmT cells) of acute leukemia patients were analyzed by flow cytometry. One hundred, thirty-one (95 AML, 25 ALL, 11 ABL) patients were studied. The leukemic cell IL-4 level was highest in the monocytic AML group (1735 ± 1056) and lowest in the dysplastic AML group (960 ± 545). The IFN-{gamma} level was highest in the acute promyelocytic leukemia (APL) group (495 ± 159), and lowest in the ALL group (252 ± 119). The IL-10 level was not significantly different among the diagnosis groups. In bmT cells, the IL-10 level was highest in the dysplastic AML group (972 ± 1049) and lowest in the APL group (397 ± 352). The leukemic cell cytokine levels were lowest and bmT cell cytokine levels were highest in the dysplastic AML group. There were no significant correlations of these cytokine levels with 2-yr survival rate, complete remission (CR) rate, or relapse rate. The cytokine levels of bmT cells at the time of CR became normal and were not different among the diagnosis groups. In summary, leukemic cell and bmT cell cytoplasmic expression profiles of IL-4, IL-10, and IFN-{gamma} are characteristic for each diagnostic group of acute leukemia patients and the profiles of bmT cells are normal at the time of CR.

Keywords: IL-4, IL-10, IFN-{gamma}, acute leukemia, T lymphocyte, bone marrow T cells


   Introduction
Top
 Abstract
 Introduction
Materials and Methods
 Results
 Discussion
 Acknowledgement
 References
 
Acute leukemia is a progressive clonal disorder that is driven by mutations [1–3]. Hyperactive immune response and immune inactivity have both been emphasized in the pathogenesis of acute leukemia [3–6]. Cytokines are secreted by particular cell types in response to a variety of stimuli and the cytokines regulate the immune responses and many other biologic processes [7]. However, the roles of cytokines in the pathogenesis of acute leukemia have not been thoroughly elucidated. In acute leukemia patients, cytokines could be produced both by leukemic and normal cells, including T lymphocytes, and the cytokine production could be associated with the lineage commitment and differentiation of the leukemic cells, as well as with the patients’ prognosis [8,9]. Cytokines have been reported to be important regulators of AML blast proliferation, but the responses to cytokines have been variable [10]. The function of interleukin-4 (IL-4) in acute leukemia is controversial [11–14]. IL-10 has been detected in the leukemic cells of most ALL and AML cases and it suppresses the immune reactions, suggesting that IL-10 could be associated with escape of leukemia cells from immune surveillance [15–19]. Gamma interferon (IFN-{gamma}) has been suggested to influence immune surveillance in B-cell ALL [8].

The cytokines produced by T lymphocytes are critical for the effectiveness of immune responses. However, the intracellular cytokine levels of T lymphocytes have been reported to be variable in patients with various malignant tumors [14,20,21]. In acute leukemia, the effects of intracellular cytokine levels of T lymphocytes on immune functions are controversial [22–25]. Since most cytokines act locally over short distances, the lymphocytes in the bone marrow that are admixed with leukemic cells could play a more important role in anti-leukemic immunity than the lymphocytes in the peripheral blood, because bone marrow lymphocytes increase the availability of cytokines at the target site [26]. However, the levels of intracellular cytokines in bone marrow lymphocytes of acute leukemia patients have not been studied. It is possible that cytokine levels of the bone marrow T lymphocytes (bmT cells) return to normal after eradication of the leukemia cells from the bone marrow, as in a complete remission state, if the leukemic cells stimulate the T cells.

In the present study, the cytoplasmic levels of IL-4, IL-10, and IFN-{gamma} were measured in leukemic cells and bmT cells of acute leukemia patients at the time of their initial diagnosis. In addition, the cytokine profiles of bmT cells were measured after chemotherapy during complete remission to gain insight into the biology of acute leukemia.


   Materials and Methods
Top
 Abstract
 Introduction
 Materials and Methods
Results
 Discussion
 Acknowledgement
 References
 
Patients.  One hundred, thirty-one patients (age 2 to 76 yr, 76 males, 55 females) who presented with acute leukemia at St. Mary’s Hospital from July 2002 to August 2003 (95 AML, 25 ALL, 11 ABL) were investigated (Table 1Go). The diagnostic criteria were based on the FAB classification; the patients were grouped into the AML, ALL, and acute biphetotypic/bilineal leukemia (ABL) groups. ABL was diagnosed when the blasts had morphologic and/or immunophenotypic characteristics of both myeloid and lymphoid cells [27,28]. The AML cases were grouped into 4 categories: AML cases with mainly myeloblasts (M0, M1, M2) were grouped as the myeloblastic AML group; AML cases with a significant proportion of monocytic leukemic cells (M4, M5) were grouped as the monocytic AML group; acute promyelocytic leukemia (APL) cases were grouped as the APL group; and acute erythro-leukemia and AML cases with multilineage dysplasia were grouped as the dyspoietic AML group.


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  		Table 1. The clinical characteristics of the patients with acute leukemia.
 
The chemotherapy regimen used for the AML patients was IDA with BHAC (3 x 7); a modified hyper-CVAD regimen was used for the ABL and ALL patients. There were no significant differences in clinical courses, including the complete remission (CR) rate, the 2-yr survival rate, or the relapse rate after CR, among the different diagnosis groups, except that there was higher 2-yr survival rate (84.6%) in the APL group (Table 1Go, p >0.05). The 2-yr survival rate was different in the CR group vs the no remission group, and in the relapsed group vs the no relapse group.

The bone marrow samples taken at the time of initial presentation were used. Paired post-chemotherapy samples at the time of CR, in addition to the initial samples, were collected from 44 patients. Normal bone marrow samples from 11 donors of bone marrow for transplantation were used as controls.

All of the patients and donors gave informed written consent prior to the specimen collection for the investigative use of any specimen that remained after their routine laboratory tests. The EDTA-anti-coagulated bone marrow aspiration samples were analyzed within 2 hr after collection. The samples were kept at room temperature (18°C to 20°C) until they were analyzed.

Comparative quantitative analysis of intracellular cytokines.  Intracellular cytokine levels were evaluated by flow cytometry as described previously [29]. Briefly, 20 µl of FITC conjugated anti-CD3 (Becton Dickinson, San Jose, CA) antibody was added to 50 µl of the well-mixed bone marrow aspirate. The mixture was then incubated in the dark at room temperature for 15 min, and erythrocytes were lysed with lysing solution (Becton Dickinson). The cells were fixed and permeabilized using a Cytofix/Cytoperm kit (BD Pharmingen, San Diego, CA) according to the manufacturer’s instructions. PE-conjugated antibodies to human IL-4, IL-10, and IFN-{gamma} were purchased from Serotec Ltd. (Oxford, UK). Ten µl of antibodies to human IL-4, IL-10, and IFN-{gamma} were added to each tube and incubated for 30 min at 4°C. After washing with the perm/wash solution supplied with the kit, the cells were analyzed by flow cytometry (FACS-Calibur, Becton Dickinson) using the CellQuest program. QuantiBRITE beads (Becton Dickinson) were tested as a reference sample.

Lymphocytes showing CD3 positive signals were gated for analysis of bmT cells; gates for leukemic cells were set using forward- and side-scattering characteristics according to the type of leukemia (Fig. 1Go). The results were expressed as geometric mean fluorescence intensitites, and the mean number of bound PE molecules per cell was calculated by the QuantiQuest program (Becton Dickinson) [30]. Briefly, an equation was constructed by the QuantiQuest program using the mean fluorescence intensities of QuantiBRITE beads and the known number of bound PE molecules per bead. The mean number of bound PE molecules per cell was calculated using this equation and the QuantiQuest program.


Figure 1
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  		Fig. 1. Dot scattergrams of leukemic cells and bone marrow T lymphocytes of acute erythroleukemia (1a,b) and acute promyelocytic leukemia (2a,b) after staining with anti-IL-4-PE. Leukemic cells of acute promyelocytic leukemia show more expression of IL-4 than acute erythroleukemia. The bone marrow T lymphocytes at the time of initial diagnosis (3a) express more IL-10 than at the time of complete remission (3b).

 
Statistical analysis.  Comparisons among the patients of each diagnosis group were made by the Kruskal-Wallis test, and the amounts of intracellular cytokines between groups (survived vs deceased groups, CR vs no remission groups, relapsed vs no relapse groups, and patients vs controls) were compared by the Mann-Whitney U test and SPSS program. Clinical characteristics in diagnosis groups were analyzed by Chi-square test. Pearson’s correlation coefficient was used to assess correlations between cytokine levels and to compare initial cytokine levels to those after chemotherapy. Cytokine levels of bmT cells before and after chemotherapy were evaluated by the Wilcoxon signed-rank test.


   Results
Top
 Abstract
 Introduction
 Materials and Methods
 Results
Discussion
 Acknowledgement
 References
 
The intracellular cytokine levels (number of bound PE molecules/cell) in each diagnosis group of patients are shown in Fig. 1Go. The leukemic cell IL-4 level of acute leukemia averaged 1408 (SD ± 927), and was highest in the monocytic AML group (1735 ± 1056) and lowest in the dyspoietic AML group (960 ± 545); there was a significant difference among diagnosis groups (p = 0.048). The leukemic cell IL-10 level of acute leukemia averaged 1294 ± 741, and there was no significant difference among diagnosis groups (p = 0.182). The leukemic cell IFN-{gamma} level of acute leukemia averaged 398 ± 228, and was highest in the APL group (495 ± 158) and lowest in the ALL group (252 ± 119); there was a significant difference among the diagnosis groups (p <0.001).

The bmT cell IL-4 and IL-10 levels at the time of initial diagnosis were higher than the normal controls (p <0.05); the IFN-{gamma} level was also higher than the normal controls, but the elevation was statistically insignificant (p = 0.107) (Table 2Go). The bmT cell IL-4 and IFN-{gamma} levels showed no difference among the diagnosis groups (p >0.05). However, the bmT cell IL-10 level was highest in the dyspoietic AML group (972 ± 1049) and lowest in the APL group (397 ± 352); there was a significant difference among the AML groups (p = 0.035). The intracellular levels of all 3 types of cytokines were lowest in leukemic cells; those of the bmT cells were highest in the dyspoietic AML group among the AML groups (Fig. 2Go).


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  		Table 2. Bone marrow T lymphocyte intracellular cytokine levels at the time of diagnosis and at the time of complete remission in acute leukemia patients.
 

Figure 2
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  		Fig. 2. The intracellular cytokine levels in diagnosis groups of acute leukemia patients. DX1: AML M0, M1, M2; DX2: AML M4 & M5; DX3: APL; DX4: acute erythroleukemia and AML with multilineage dysplasia; DX5: acute biphenotypic/bilineal leukemia; DX6: acute lymphoblastic leukemia. IL-4BL & IL-10BL & IFNBL: expression levels of IL-4, IL-10, and IFN-{gamma} of leukemic cells; IL-4LYM & IL-10LYM & IFNLYM: expression levels of IL-4, IL-10, and IFN-{gamma} of bone marrow T lymphocytes at the time of initial diagnosis.

 
Correlations of leukemic cell cytokine levels and bmT cell cytokine levels are presented in Table 3Go. The levels of the 3 cytokines in the leukemic cells were closely correlated (r >0.7, p <0.001), and the levels of the 3 cytokines in bmT cells at the time of initial diagnosis were also correlated (r >0.6, p <0.001). Correlations of leukemic cell cytokine levels vs bmT cell cytokine levels were weak (r <0.6). The cytokine levels were not significantly correlated with patients’ age (p >0.05).


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  		Table 3. Correlations of the leukemic cell intracellular cytokine levels vs the bone marrow T lymphocyte intracellular cytokine levels at the time of initial diagnosis (correlation coefficients, p values in parentheses).*
 
The leukemic cell and bmT cell cytokine levels at the time of the initial diagnosis in each group of patients, along with the clinical courses, are presented in Table 3Go. The IL-4 levels of the leukemic cells in the >2-year survivor group was 1489 ± 908, which was higher than the deceased group (1297 ± 964), but this elevation was insignificant (p =0.065). The IL-10 level of leukemic cells of the >2-year survivor group was 1312 ± 565, which was also higher than the deceased group (1171 ± 757), but this elevation was also insignificant (p = 0.076). The IFN-{gamma} level of the leukemic cells was similar is the survivor and deceased groups (p = 0.338). There were no significant differences in cytokine levels of the leukemic cells in the CR group vs the no remission group, or in the relapsed group vs the no relapse group (p >0.05).

There were no significant differences in the intracellular cytokine levels of the bmT cells at the time of initial diagnosis in the survivor vs deceased groups, the CR vs no remission groups, or the relapsed vs no relapse groups (p >0.05). The cytokine levels of bmT cells at the time of CR after chemotherapy were significantly decreased when compared to the levels at the time of initial diagnosis (Table 4Go, Fig. 1Go). The mean difference of IL-4 was 207 ± 148 (p = 0.002); that of IL-10 was 168 ± 72 (p = 0.004); that of IFN-{gamma} was 35 ± 19 (p = 0.012). These levels were similar to those of bmT cells in the normal bone marrow, IL-4: 260 ± 118, IL-10: 258 ± 104, and IFN-{gamma}: 91 ± 34 (p >0.05). The cytokine levels of bmT cells after chemotherapy were not significantly different among the 6 diagnosis groups (Table 2Go, p >0.05). The cytokine levels of bmT cells at the time of CR after chemotherapy or the differences before and after chemotherapy were not correlated with the 2-yr survival rate or the relapse rate (p >0.05).


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  		Table 4. Leukemic cell intracellular cytokine levels and bone marrow T lymphocyte intracellular cytokine levels at the time of initial diagnosis and after chemotherapy in groups of patients with specified clinical courses (means ± SD; p-values).*
 

   Discussion
Top
 Abstract
 Introduction
 Materials and Methods
 Results
 Discussion
Acknowledgement
 References
 
IL-4 has been reported to have antitumor effects and to suppress the growth of ALL cells; IL-4-producing T lymphocytes enhance the in vitro proliferation of leukemic cells, and in particular, the AML subset [31–33]. However, the in vitro effects of IL-4 and IL-10 do not necessarily reflect their in vivo effects [34], and the leukemic cell cytoplasmic IL-4 level in acute leukemia has not been studied before. The expression of distinct cytokines, including IL-10 and IFN-{gamma}, has been reported to be associated with lineage commitment and differentiation of the leukemic cells [8,9]. In this study, the leukemic cell IL-4 level was highest in the AML group having a monocytic component and was lowest in the dyspoietic AML group, and there were significant differences among the diagnosis groups (p = 0.048). However, there were no significant differences in the leukemic cell IL-10 levels among the diagnosis groups (p = 0.182). That suggests that IL-4, rather than IL-10, is associated with lineage differentiation. The leukemic cell IFN-{gamma} level was highest in the APL group and lowest in the ALL group and there were significant differences among the 6 diagnosis groups (p <0.001).

There has been no previous report about cytokine expression profiles of leukemic cells according to diagnosis groups. The results of the present study suggest that the leukemic cells have characteristic expression patterns of cytoplasmic cytokines according to the type of acute leukemia. In AML, leukemic cells can be induced by cytokines (eg, IL-4) to differentiate into dendritic cells that are effective at antigen presentation [35–37]. Higher expression of IL-10 and IFN-{gamma} has been reported in the good prognosis group [8,9]. However, in another study, capability of autocrine proliferation was reported to be an adverse prognostic factor in AML patients [10]. In this study, the IFN-{gamma} level of leukemic cells was similar in the survivor vs deceased groups (p = 0.338), and although the elevations were statistically insignificant (p >0.05), IL-4 and IL-10 were expressed more in the 2-yr survivor group with AML.

Intracellular cytokine-producing T lymphocyte subsets in the peripheral blood have been reported to be increased in patients with ALL, AML, and malignant lymphoma [29,38,39]. The T lymphocytes showed release of IL-4, IL10, and IFN-{gamma} in the presence of ALL and AML blasts that act as accessory cells [23,24]. T lymphocyte proliferation and cytokine release showed wide variation within the ALL patients, but these differences in co-stimulatory function were not related to the release of cytokines by the blasts [23,25]. In the present study, the bmT cell IL-4 and IFN-{gamma} levels revealed no significant differences among the 6 diagnosis groups (p >0.05). However, it is interesting that leukemic cell cytokine levels were lowest and bmT cell cytokine levels were highest in the dyspoietic AML group. These patients had the worst prognosis, including the lowest CR rate and the lowest 2-yr survival rate. The bmT cell cytokine levels were lowest in the APL group, and this group showed the highest 2-yr survival rate. However, the bmT cell cytokine levels were not significantly different according to the prognosis within the same diagnosis group (p >0.05). This indicates that the bmT cell cytokine levels reflect the type of leukemia rather than the prognosis of the individual leukemia patient. Different cell types respond differently to cytokines [40]. Therefore, characteristic cytokine expression profiles of the different types of acute leukemia could help to explain their different behaviors. The IL-4, IL-10, and IFN-{gamma} expressions were correlated with each other. It is possible that the control mechanisms for expression of these 3 cytokines are likewise related to each other.

The cytokine levels of bmT cells at the time of CR after chemotherapy were decreased significantly, compared to the cytokine levels of the bmT cells before the start of chemotherapy; they were not significantly different among the diagnosis groups and were unrelated to the 2-yr survival rate. There has been no previous report about levels of these bmT cell cytokines after chemotherapy for acute leukemia. Our results suggest that the cytokine levels of bmT cells change in response to the leukemic cells in the bone marrow and are normalized when the leukemic cells are eradicated from the bone marrow.

In conclusion, the leukemic cell and bmT cell cytoplasmic expression profiles of IL-4, IL-10, and IFN-{gamma} are characteristic for each diagnostic group of acute leukemia and the cytokine expression profiles of the bmT cells are normalized at the time of CR after chemotherapy. These results may contribute to research on immunotherapy using T lymphocytes and cytokines in patients with acute leukemia.


   Acknowledgement
Top
 Abstract
 Introduction
 Materials and Methods
 Results
 Discussion
 Acknowledgement
References
 
This study was supported by a grant (02-PJ1-PG10-20801-0004) from the Korea Health 21 Research and Development Project, Ministry of Health and Welfare, Republic of Korea.


   References
Top
 Abstract
 Introduction
 Materials and Methods
 Results
 Discussion
 Acknowledgement
 References
 

  1. Lichtman MA, Liesveld JL. Acute myelogenous leukemia. In: Williams’ Hematology, 6th ed (Beutler E, Lichtman MA, Coller BS, Kipps TJ, Seligsohn U, Eds), McGraw-Hill, New York, 2001; vol 2, p 1047.
  2. Pui CH. Acute lymphoblastic leukemia. In: Williams’ Hematology, 6th ed (Beutler E, Lichtman MA, Coller BS, Kipps TJ, Seligsohn U, Eds), McGraw-Hill, New York, 2001; vol 2, p 1141.
  3. Greaves, M.F. Aetiology of acute leukaemia. Lancet 1997;349:344–349.[Medline]
  4. Hersh EM, Whitecar JP, McCredie KB, Bodey GP, Freireich EJ. Chemotherapy, immunocompetence, immunosuppression and prognosis in acute leukemia. NEJM 1971;285:1211–1216.[Medline]
  5. Mackall CL. T-cell immunodeficiency following cyto-toxic anti-neoplastic therapy: a review. Stem Cells 2000; 18:10–18.[Medline]
  6. Narita M, Takahashi M, Liu A, Nikkuni K, Furukawa T, Toba K, Koyama S, Takai K, Sanada M, Aizawa Y. Leukemia blast-induced T-cell anergy demonstrated by leukemia-derived dendritic cells in acute myelogenous leukemia. Exp Hematol 2001;29:709–719.[Medline]
  7. Shin GS, Lee BH, Lee S, Chung SY, Kim M, Lim J, Kim Y, Kwon HJ, Kang CS, Han K. Monokine levels in cancer and infection. Ann Clin Lab Sci 2003;33:149–155.[Abstract/Free Full Text]
  8. Cloppenborg T, Stanulla M, Zimmermann M, Schrappe M, Welte K, Klein C. Immunosurveillance of childhood ALL: polymorphic interferon-gamma alleles are associated with age at diagnosis and clinical risk groups. Leukemia 2005;19:44–48.[Medline]
  9. Wu S, Gessner R, von Stackelberg A, Kirchner R, Henze G, Seeger K. Cytokine/cytokine receptor gene expression in childhood acute lymphoblastic leukemia: correlation of expression and clinical outcome at first disease recurrence. Cancer 2005;103:1054–1063.[Medline]
  10. Bruserud O. IL-4, IL-10 and IL-13 in acute myelogenous leukemia. Cytokines Cell Mol Ther 1998;4:187–198.[Medline]
  11. Okabe M, Kuni-eda Y, Sugiwura T, Tanaka M, Miyagishima T, Saiki I, Minagawa T, Kurosawa M, Itaya T, Miyazaki T. Inhibitory effect of interleukin-4 on the in vitro growth of Ph1-positive acute lymphoblastic leukemia cells. Blood 1991;78:1574–1580.[Abstract/Free Full Text]
  12. Pandrau D, Saeland S, Duvert V, Durand I, Manel AM, Zabot MT, Philippe N, Banchereau J. Interleukin 4 inhibits in vitro proliferation of leukemic and normal human B cell precursors. J Clin Invest 1992;90:1697–1706.[Medline]
  13. Manabe A, Coustan-Smith E, Kumagai M, Behm FG, Raimondi SC, Pui CH, Campana D. Interleukin-4 induces programmed cell death (apoptosis) in cases of high-risk acute lymphoblastic leukemia. Blood 1994; 83:1731–1737.[Abstract/Free Full Text]
  14. Dancescu M, Rubio-Trujillo M, Biron G, Bron D, Delespesse G, Sarfati M. Interleukin 4 protects chronic lymphocytic leukemic B cells from death by apoptosis and upregulates Bcl-2 expression. J Exp Med 1992;176:1319–1326.[Abstract/Free Full Text]
  15. Wu S, Gessner R, Taube T, von Stackelberg A, Henze G, Seeger K. Expression of interleukin-10 splicing variants is a positive prognostic feature in relapsed childhood acute lymphoblastic leukemia. J Clin Oncol 2005;23:3038–3042.[Abstract/Free Full Text]
  16. Schulz U, Munker R, Ertl B, Holler E, Kolb HJ. Different types of human leukemias express the message for TNF-alpha and interleukin-10. Eur J Med Res 2001; 6:359–363.[Medline]
  17. Kebelmann-Betzing C, Korner G, Badiali L, Buchwald D, Moricke A, Korte A, Kochling J, Wu S, Kappelmeier D, Oettel K, Henze G, Seeger K. Characterization of cytokine, growth factor receptor, costimulatory and adhesion molecule expression patterns of bone marrow blasts in relapsed childhood B cell precursor ALL. Cytokine 2001;13:39–50.[Medline]
  18. Salazar-Onfray F. Interleukin-10: a cytokine used by tumors to escape immunosurveillance. Med Oncol 1999;16:86–94.[Medline]
  19. Zeidler R, Eissner G, Meissner P, Uebel S, Tampé R, Lazis S, Hammerschmidt W. Downregulation of TAP1 in B lymphocytes by cellular and Epstein-Barr virus-encoded interleukin-10. Blood 1997;90:2390–2397.[Abstract/Free Full Text]
  20. Mainou-Fowler T, Taylor PR, Miller S, Dickinson AM, Proctor SJ. Intracellular cytokine profiles by peripheral blood CD3+ T-cells in patients with classical Hodgkin lymphoma. Leuk Lymphoma 2003;44:1325–1331.[Medline]
  21. Mainou-Fowler T, Miller S, Proctor SJ, Dickinson AM. The levels of TNF alpha, IL4 and IL10 production by T-cells in B-cell chronic lymphocytic leukaemia (B-CLL). Leuk Res 2001;25:157–163.[Medline]
  22. Brunda MJ, Luistro L, Hendrzak JA, Fountoulakis M, Garotta G, Gately NK. Role of interferon-gamma in mediating the antitumor efficacy of interleukin-12. J Immunother Emphasis Tumor Immunol 1995;17:71–77.[Medline]
  23. Bruserud O, Ulvestad E. Human acute lymphoblastic leukemia (ALL) blasts as accessory cells during T-cell activation: differences between patients in costimulatory capacity affect proliferative responsiveness and cytokine release by activated T cells. Cancer Immunol Immunotherap 2003;52:215–225.
  24. Bruserud O, Ulvestad E. Acute myelogenous leukemia blasts as accessory cells during in vitro T lymphocyte activation. Cellular Immunology 2000; 206:36–50.[Medline]
  25. Zhang XL, Komada Y, Chipeta J, Li QS, Inaba H, Azuma E, Yamamoto H, Sakurai M. Intracellular cytokine profile of T cells from children with acute lymphoblastic leukemia. Cancer Immunol Immunother 2000;49:165–172.[Medline]
  26. Sayers TJ, Brooks AD, Seki N, Smyth MJ, Yagita H, Blazer BR, Malyguine AM. T cell lysis of murine renal cancer: multiple signaling pathways for cell death via Fas. J Leukocyte Biol 2000;68:81–86.[Abstract/Free Full Text]
  27. EGIL. The value of c-kit in the diagnosis of biphenotypic acute leukemia. Leukemia 1998;12:2038.[Medline]
  28. Bene MC, Bernier M, Castodi G, Knapp W, Ludwig WD, Matutes E, Orfao A, van’t Veer MB. Proposals for the immunological classification of acute leukaemias. Leukemia 1995;9:1783–1786.[Medline]
  29. Panoskaltsis N, Reid CD, Knight SC. Quantification and cytokine production of circulating lymphoid and myeloid cells in acute myelogenous leukaemia. Leukemia 2003;17:716–730.[Medline]
  30. Lee KY, Suh BG, Kim JW, Lee W, Kim SY, Kim YY, Lee J, Lim J, Kim M, Kang CS, Han K. Varying expression levels of colony stimulating factor receptors in disease states and different leukocytes. Exp Mol Med 2000; 32:210–215.[Medline]
  31. Rossi FM, Degan M, Mazzocco FT, Di Francia R, Aldinucci D, Poletto D, Vellenga E, Pinto A, Gattei V. Co-expression of CD30 ligand and interleukin 4 (IL-4) receptors by acute myeloid leukaemia blasts is associated with the expansion of IL-4-producing CD30+ normal T cells. Br J Haematol 2002;117:59–69.[Medline]
  32. Srivannaboon K, Shanafelt AB, Todisco E, Forte CP, Behm FG, Raimondi SC, Raimondi SC, Pui CH, Campana D. Interleukin-4 variant (BAY 36–1677) selectively induces apoptosis in acute lymphoblastic leukemia cells. Blood 2001;97:752–758.[Abstract/Free Full Text]
  33. Carwell EA, Old LJ, Kassel RL. An endotoxin induced serum factor that causes necrosis of tumors. PNAS USA 1975;72:3666–3670.[Abstract/Free Full Text]
  34. Tao M, Li B, Nayini J, Sivaraman S, Song S, Larson A, Toofanfard M, Chen H, Venugopal P, Preisler HD. In vivo effects of IL-4, IL-10, and amifostine on cytokine production in patients with acute myelogenous leukemia. Leuk Lymphoma 2001;41:161–168.[Medline]
  35. Claxton D, Kao SF. Autologous immunotherapy for human leukemias. Blood Cells Mol Dis 2003;31:121–124.[Medline]
  36. Rigolin GM, Della Porta M, Bigoni R, Tieghi A, Cuneo A, Castoldi G. Dendritic cells in acute promyelocytic leukaemia. Br J Haematol 2001;114:830–833.[Medline]
  37. Narita M, Takahashi M, Liu A, Ayres F, Satoh N, Abe T, Nikkuni K, Furukawa T, Toba K, Aizawa Y. Generation of dendritic cells from leukaemia cells of a patient with acute promyelocytic leukaemia by culture with GM-CSF, IL-4 and TNF-alpha. Acta Haematol 2001;106:89–94.[Medline]
  38. Gergely L, Aleksza M, Váróczy L, Ponyi A, Sipka S, Illés Á, Szegedi G. Intracellular IL-4/INF-gamma producing peripheral T lymphocyte subsets in B cell non-Hodgkin’s lymphoma patients. Eur J Haematol 2004;72:336–341.[Medline]
  39. Luczynski W, Stasiak-Barmuta A, Krawczuk-Rybak M, Malinowska I, Matysiak M, Mitura-Lesiuk M, Kowalczyk J, Jeromin A. Th1/Th2 balance in acute lymphoblastic leukemia in children. Przegl Lek 2004;61:919–923.[Medline]
  40. Rath PC, Aggarwal BB. TNF-induced signaling in apoptosis. J Clin Immunol 1999;19:350–364.[Medline]



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