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Query: UNIPROT:P14784 (IL-2 receptor)
 3,849 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Interleukin-1 alpha (IL-1 alpha), interleukin-1 beta (IL-1 beta) and soluble IL-2 receptor (sIL-2R) serum levels were evaluated in 24 hairy cell leukemia (HCL) patients. Of these, three patients were studied at the time of diagnosis, 12 in relapse after interferon (IFN) therapy, eight with a partial response after IFN and one with a complete response after 2-deoxycoformycin (DCF) therapy. Statistically significant differences were observed in the serum levels of IL-1 beta and sIL-2R between HCL patients and controls. These were 400.3 pg per 0.1 ml (range 23.2-990) and 64.3 pg per 0.1 ml (20-115) for IL-1 beta and 4667.2 U/ml (488-7800) and 424.3 U/ml (188-666) for sIL-2R, respectively. In contrast, IL-1 alpha measurements showed no statistical differences between the two groups. A significant increase of sIL-2R (p = 0.01) and IL-1 beta (p = 0.03) serum levels was observed in patients studied at the time of diagnosis or in relapse compared to those in partial or complete remission. IL-1 beta serum levels directly correlated with sIL-2R (p less than 0.0001) and with hairy cell (HC) bone marrow infiltration, expressed by the HC index (p = 0.003). The comparison of IL-1 beta serum levels of HCL patients with those detected among 149 patients grouped according to diagnosis (Hodgkin's disease = 17, non-Hodgkin's lymphomas = 57, acute non-lymphoid leukemia = 46, and acute lymphoid leukemia = 29) indicate that HCL patients showed the highest IL-1 beta serum level increase, indicating that IL-1 beta could be used as a specific clinical marker of this disease.
Leukemia 1991 Jul
PMID:Serum interleukin-1 beta levels correlate with neoplastic bulk in hairy cell leukemia. 207 45

We studied the role of interleukin-2 (IL-2) receptor subunits in the activation of leukemic CD3+ large granular lymphocytes (LGL). Peripheral blood mononuclear cells from four patients with CD3+ LGL leukemia were activated with 500 mu/ml of recombinant IL-2. Induction of both proliferative and cytotoxic functions by IL-2 was blocked by addition of anti-p75 IL-2 receptor monoclonal antibody, but not by addition of anti-p55 IL-2 receptor monoclonal antibody. Sorting experiments demonstrated directly that the effects of the anti-p75 IL-2 receptor monoclonal antibody were on leukemic LGL. These results show constitutive expression of functional p75 IL-2 receptors on leukemic LGL and suggest a possible mechanism for leukemic LGL proliferation in vivo.
Leukemia 1990 Dec
PMID:Activation of leukemic large granular lymphocytes by interleukin-2 via the p75 interleukin-2 receptor. 214 47

Cell line PER-315 was established from a bone marrow sample of a 5-year-old boy diagnosed with acute lymphoblastic leukemia (ALL) of T cell lineage. PER-315 cells express the surface markers present on immature thymocytes, express cytoplasmic CD3, and their growth is dependent on interleukin-2 (IL-2). Hence, this cell line represents a new type of precursor T-ALL, which is IL-2 dependent. Assessment of the T cell receptor rearrangements confirmed the clonal origin of cell line PER-315, and comparison with the patient's leukemia cells revealed an identical pattern. PER-315 cells show strong cytotoxicity against cell lines K562, Daudi, and Molt-4. They do not express the Tac antigen, but bind IL-2 with a Kd of 650 pM. Since PER-315 cells represent immature thymocytes, this new cell line may provide a model to further investigate the IL-2 receptor structure present at this stage of T cell differentiation.
Leukemia 1990 Apr
PMID:Characterization of an interleukin-2 dependent human leukemic cell line, PER-315, with an immature T cell phenotype which does not express the tac antigen. 216 20

Malignant cells of a patient with acute leukemia expressed hematopoietic stem cell antigens such as CD34 and HLA-class II but lacked lineage specific differentiation markers. The leukemic blasts differentiated into mature T cells within 14 days in the presence of a T cell conditioned medium or with a mixture of highly purified interleukin-2 (IL-2) plus recombinant interleukin-3 (IL-3) and recombinant granulocyte/macrophage colony-stimulating factor (GM-CSF). Phenotypically, the maturing cells acquired the T cell-specific differentiation antigens CD2, CD3, and CD8, whereas immature differentiation antigens such as CD34 and Leu19 as well as HLA-class II and the IL-2 receptor CD25 were concomitantly down-regulated within 14 days of in vitro culture. This in vitro maturation involved two to three synchronized cell divisions. Beyond 10 days of culture the leukemic cells produced mRNA specific for the T cell receptor beta and alpha chain, but at no time transcription of T cell receptor gamma chain-specific message was detectable. To our knowledge, these data represent the first in vitro model demonstrating the differentiation of phenotypically mature T cells from immature leukemic cells induced by the combined activities of IL-2 plus IL-3 and GM-CSF.
Leukemia 1988 May
PMID:Generation of mature CD3+ and T cell receptor (TCR) + T cells from a leukemic analogue of the putative human stem cell by T cell conditioned medium containing IL-3, IL-2, and GM-CSF. 245 58

Binding of interleukin-2 (IL-2) to high affinity receptors on activated normal T cells was shown to be the essential step in induction of proliferation of such cells. The finding of abundant IL-2 receptors on malignant T cells in adult T cell leukemia suggested a deregulation of the IL-2/IL-2 receptor system and was assumed to account for aberrant growth in malignant disorders of T cells. In this study we use malignant T cells from nine patients with the clinical diagnosis of T-ALL or T-NHL and did not detect IL-2 dependent growth under conditions in which normal T cells responded to IL-2. IL-2 receptors comparable in numbers to activated T cells were found on T-ALL/T-NHL cells stimulated with PHA and PMA. However, binding studies using radiolabeled IL-2 indicated that the receptors present on malignant T cells were not able to bind to IL-2 with high affinity. Therefore, if IL-2 is involved in the proliferation of malignant T cells, its mechanism of growth regulation may be different from the one for normal T cells. Alternatively, IL-2 may not play a role in the regulation of growth of malignant T cells in vitro.
Leukemia 1989 Aug
PMID:Lack of interleukin-2 (IL-2) dependent growth of TAC positive T-ALL/NHL cells is due to the expression of only low affinity receptors for IL-2. 278 51

In this paper we communicate that cells of a selected B-CLL clone (I83), after 2 days of Staphylococcus aureus Cowan strain 1 (SAC) activation, respond to recombinant IL-2 (rIL-2) and a B cell stimulatory factor (BSF-MP6) and act in strong synergism with induction of simultaneous high-rate proliferation and differentiation. None of the factors alone or other lymphokines (IFN-gamma, TNF-alpha, 12 kDa BCGF, IL-1, IL-4, IL-5, IL-6) induced significant DNA synthesis in SAC-activated cells. However, low levels of IgM were produced by cells stimulated by SAC + rIL-2. The SAC activation was followed by an increase in IL-2 receptor (IL-2R; CD25) expression, and the proliferation induced by BSF-MP6 + rIL-2 could be blocked in a dose-dependent manner by alpha-CD25 antibody. Furthermore, flow cytometric cell cycle studies showed that SAC and BSF-MP6 + rIL-2 stimulated cells underwent a complete transition through the cell cycle to become arrested in G1. The induced proliferation by BSF-MP6 + rIL-2 was dependent on serum but independent of the 2.8% of CD4, CD8, CD14, and CD16 positive cells contaminating the I83 cell population. Previously, we reported that I83 cells activated by 12-O-tetradecanoylphorbol-13-acetate (TPA) were induced to differentiation only but that the addition of BSF-MP6 induced DNA synthesis concomitantly with the differentiation. This paper demonstrates that physiological stimuli can induce both high-rate proliferation and differentiation in a B-CLL clone in vitro. It also suggests that the low proliferation and the differentiation block in vivo, characteristic of most B-CLLs, may reflect a subnormal response of B-CLL cells to growth and differentiation factors, or a dysfunction in the factor production by the patients' T cells.
Leukemia 1989 Aug
PMID:Interleukin-2 and a T cell hybridoma (MP6) derived B cell-stimulatory factor act synergistically to induce proliferation and differentiation of human B-chronic lymphocytic leukemia cells. 217 41

The establishment of IL-2-independent T-cell lines spontaneously derived from long-term IL-2-dependent cytotoxic T-cell lines is described. Two lines (cloned and uncloned) studied in detail have shown the following characteristics: (1) Permanent loss of IL-2 dependence. (2) Partial or complete loss of both cytotoxic activity and the IL-2 receptor. (3) Increased expression of T-cell membrane markers (Thy1.2, Lyt1.2) compared with the parental line. (4) Lower level of DNA methylation than in freshly obtained lymphoid cells. (5) Different karyotypic pattern from the parental IL-2-dependent line, with a mean number of 39-40 chromosomes and a resemblance to T leukemic lines. (6) Leukemia caused in normal syngeneic C57BL/6 mice by the uncloned line, in contrast to the cloned IL-2-independent line or the parental dependent line. Unlike established leukemic lines, however, the independent line gave rise to tumors which regressed in some mice within a few days of their appearance. These findings suggest that T-cell lines maintained with IL-2 for prolonged periods of time (greater than 3 months) can undergo transformation and, therefore, should not be utilized for immunotherapeutic purposes.
 ...
PMID:Characterization of a tumorigenic murine T-lymphoid-cell line spontaneously derived from an IL-2-dependent T-cell line. 308 91

Tumor cells from 5 human B cell non-Hodgkin's lymphoma (B-NHL) patients were investigated for proliferative activity and idiotypic (Id+) immunoglobulin (Ig) secretion in serum-free medium without deliberate addition of B cell growth or differentiation factors (BCDF). These data were compared with cell surface marker expression, notably of activation antigens such as 4F2 and interleukin-2 (IL-2) receptor. Cells from all patients became 4F2 positive at the end of the 6-day culture period. Freshly drawn cells from 3 out of 5 patients expressed the IL-2 receptor (CD25; Tac antigen) or acquired this marker during culture in vitro and secreted relatively high levels of Id+ Ig in vitro. This correlated with elevated serum Id levels (greater than or equal to 0.5 micrograms/ml in vitro versus greater than or equal to 20 micrograms/ml in vivo). In the 2 CD25 (Tac)- B-NHL patients serum Id levels were below the detection limit and the amount of Id+ Ig secreted in vitro did not surpass 50 ng/ml. Only the B-NHL cells from a single patient were initially CD25 (Tac) positive and only these cells proliferated in serum-free culture. To test whether IL-2 receptor expression in the 3 CD25 (Tac)+ patients was functional, recombinant IL-2 (rIL-2) either alone or in conjunction with BCDF and recombinant IL-4 (rIL-4) was added to the cultures. In 2 out of 3 CD25 (Tac)+ patients rIL-2 was capable of enhancing proliferation or Ig secretion. In addition rIL-2 was found to enhance BCDF-mediated but not rIL-4 mediated responses. The third CD25 (Tac)+ B-NHL population was resistant to any of these lymphokines. Thus, this serum-free culture system may accurately reflect patient serum Id levels. IL-2 appears to regulate not only the in vitro but also the in vivo Ig secretion by neoplastic B cells.
Leukemia 1988 Apr
PMID:Idiotypic immunoglobulin secretion by human B cell non-Hodgkin's lymphomas is related to the expression of the interleukin-2 receptor. 312 22

High levels of soluble IL-2 receptor (sIL-2R) are detectable in the serum of HCL patients. To determine the cell source of this molecule, we evaluated the presence of sIL-2R in the supernatants obtained from in vitro cultures of leukemic (hairy cell, HC) and non-leukemic lymphocytes from six untreated HCL patients and from an additional four patients under therapy with rIFN-alpha 2. We demonstrated that cultured HCs at resting conditions were able to spontaneously release the sIL-2R, whereas control enriched B cells did not. This phenomenon was present only when culturing HCs recovered from patients observed at the time of diagnosis but was not observed during treatment with rIFN-alpha 2. Following activation in vitro with a series of different stimulatory agents including BCGF, phorbol myristate acetate, and anti-human IgM antibody, cultured HCs increased their capability to shed the IL-2R molecules. On the other hand, the release of sIL-2R from enriched T cell populations from HCL patients did not significantly differ from the value obtained in controls. Taken together, these findings provide evidence that leukemic B cells represent the main source of sIL-2R in HCL patients and further emphasize the importance of evaluating this parameter as a relevant marker for monitoring the effectiveness of rIFN-alpha 2 therapy.
Leukemia 1988 Dec
PMID:Origin of the soluble interleukin-2 receptor in the serum of patients with hairy cell leukemia. 326 62

Since all-trans retinoic acid (ATRA) and granulocyte colony-stimulating factor (G-CSF) not only enhance proliferation and differentiation of normal myeloid cells but also synergistically promote the differentiation of myeloid leukemic blast cells in vitro, we have started a pilot study of combined treatment with ATRA and G-CSF in patients with myelodysplastic syndrome, to analyze the effect of these drugs on hematopoietic differentiation. ATRA was given at 45 mg/m2/day p.o. from week 1-12 and G-CSF at 5 micrograms/kg/day s.c. from week 5-12 with dose modifications according to the absolute neutrophil counts (ANC). A total of 15 patients, predominantly with refractory anemia, were treated. During initial ATRA therapy, a bilineage response with increases of both ANC and platelet counts occurred in three patients. During combined ATRA/G-CSF therapy, ANC increased in all patients, and platelets increased in three out of 14 evaluable patients. An increase in hemoglobin concentration and a decrease in transfusion requirements occurred in one patient each. In the bone marrow, the myeloid-to-erythroid ratio increased during ATRA treatment and remained increased during concomitant G-CSF administration, while the maturation index of myeloid cells increased only in response to ATRA therapy, but returned to baseline during ATRA/G-CSF treatment. Cytogenetic analysis demonstrated persistence of the abnormal clones in all patients. The number of circulating progenitor cells CFU-GM increased in all patients studied. Serum concentrations of the soluble TNF receptor and IL-2 receptor both increased, while TNF-alpha--already elevated prior to therapy--and soluble ICAM-1 concentrations did not significantly change. Adverse effects included dermatitis and cheilosis in most patients, and a drop in platelet counts related to G-CSF in one patient. The pilot study demonstrates that the combination treatment with ATRA/G-CSF is well tolerated, leading to normalization of ANC in most, and improvement of platelets and red blood cells in a subgroup of patients.
Leukemia 1994 Mar
PMID:Effect of combination therapy with all-trans-retinoic acid and recombinant human granulocyte colony-stimulating factor in patients with myelodysplastic syndromes. 751 Mar 54


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