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Query: UMLS:C0023418 (leukemia)
 93,477 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Hematological malignancies accompanied by eosinophilia are reviewed in relation to chromosomal changes and cytokine production. Eosinophilia accompanied by hematological malignancies can be divided into two groups. In some myelogenous leukemias, including acute myelomonocytic leukemia with eosinophilia (FAB M4Eo), acute myeloblastic leukemia (FAB M2 t(8;21)) and chronic myelogenous leukemia, neoplastic cells themselves appear to differentiate into eosinophils. On the other hand, transformed tumor cells secrete some eosinophil-stimulating cytokines, including interleukin-3, interleukin-5 and granulocyte-macrophage colony-stimulating factor and these cytokines stimulate the proliferation of normal eosinophil precursors in some lymphoid malignancies, including some types acute lymphoblastic leukemia (especially with t(5;14)) or malignant lymphoma, including Hodgkin's lymphoma and adult T cell lymphoma/leukemia.
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PMID:[Hematological malignancies with eosinophilia]. 849 61

The relationship between cytokine production patterns and immunophenotype marker profiles was studied in a panel of 18 T cell lines originating from various types of hematological malignancies and from human T cell lymphotropic virus-I (HTLV-I)-transformed cells. The production of 11 different cytokines by both unstimulated and phytohemagglutinin (PHA)-stimulated cells was tested. The production of interleukin-1 alpha (IL-1 alpha), IL-2, IL-3/granulocyte-macrophage colony stimulating factor (GM-CSF), IL-4, IL-5, IL-6, tumor necrosis factor-alpha (TNF-alpha), TNF-beta and interferon-gamma (IFN-gamma) by some of the cell lines was detected, and no cell line produced IL-1 beta or IFN-alpha. All 4 cell lines producing IL-1 alpha also produced other inflammatory cytokines, namely, IL-6, TNF-alpha and TNF-beta, but they did not produce IL-2. The IL-1 alpha-producing cell lines had the phenotype of mature, activated T cells, regardless of leukemia or transformant origin (TdT-, CD4+, CD8-, IL-2R+, HLA-DR+) and all were HTLV-1+. However, the production of other cytokines followed a random distribution, and no relationship emerged between cytokine production patterns and alpha/beta or gamma/delta type of T cell receptor (TcR) expression, immunophenotypic marker profiles, or the clinical origin of the cells. These results thus show that human leukemia and HTLV-I-transformed T cell lines can produce a large number of biologically active cytokines and that, except for the association of inflammatory cytokine production with mature activated cells, random patterns of cytokine production reflect the individuality of leukemia cell lines.
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PMID:Multiple and heterogeneous patterns of cytokine production in 18 leukemia and in vitro transformed mature T cell lines reflect the individuality of human leukemias. 849 92

An adult T cell leukemia cell line, HIL-3, constitutively secretes a factor which induces the phenotypical and functional eosinophilic differentiation of a human eosinophilic leukemia cell line, EoL-1. Biochemical characteristics of the factor, termed eosinophilic leukemia cell differentiation factor (ELDF), were examined. ELDF was precipitated by 35 to 65% saturated ammonium sulfate from the culture supernatants of HIL-3 cells (HIL-3 sup). ELDF was eluted in a peak corresponding to a molecular weight of 30 to 40 kd by gel filtration. Isoelectric focusing in the Rotofor showed that ELDF had isoelectric points of 5 to 6. ELDF was trypsin-sensitive and stable to heat treatment at 65 degrees C for 30 minutes but labile at 80 degrees C or pH lower than 3. Half of the activity adhered to lentil-lectin but not to Con-A, indicating that a part of ELDF is glycoprotein with an N-linked carbohydrate moiety, which did not seem to be essential for ELDF activity. The biochemical characteristics of ELDF and blocking experiments using cytokine-specific neutralizing antibodies suggest that ELDF is different from gamma-interferon (IFN-gamma), tumor necrosis factor-alpha (TNF-alpha), granulocyte-macrophage colony-stimulating factor (GM-CSF), interleukin-5 (IL-5) and interleukin-2 (IL-2), which may exist in HIL-3 sup, and that ELDF may be a previously unrecognized leukemia differentiation factor.
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PMID:Characterization of an eosinophilic leukemia cell differentiation factor (ELDF) produced by a human T cell leukemia cell line, HIL-3. 850 May 76

The human interleukin-3 receptor (IL-3R) is expressed on myeloid, lymphoid, and vascular endothelial cells, where it transduces IL-3-dependent signals leading to cell activation. Although IL-3R activation may play a role in hematopoiesis and immunity, its aberrant expression or excessive stimulation may contribute to pathologic conditions such as leukemia, lymphoma, and allergic reactions. We describe here the generation and characterization of a monoclonal antibody (MoAb), 7G3, which specifically binds to the IL-3R alpha-chain and completely abolishes its function. MoAb 7G3 immunoprecipitated and recognized in Western blots the IL-3R alpha-chain expressed by transfected cells and bound to primary cells expressing IL-3R alpha. MoAb 7G3 bound the IL-3R alpha-chain with a kd of 900 pmol/L and inhibited 125I-IL-3 binding to high- and low-affinity receptors in a dose-dependent manner. Conversely, IL-3 but not granulocyte-macrophage colony-stimulating factor (GM-CSF) inhibited 125I-7G3 binding to high- and low-affinity IL-3Rs, indicating that MoAb 7G3 and IL-3 bind to common or adjacent sites. In keeping with the inhibition of IL-3 binding, MoAb 7G3 antagonized IL-3 biologic activities, namely stimulation of TF-1 cell proliferation, basophil histamine release, and IL-6 and IL-8 secretion from human endothelial cells. Two other anti-IL-3R alpha-chain MoAbs failed to inhibit IL-3 binding or function. Epitope mapping experiments using truncated IL-3R alpha-chain mutants and IL-3R alpha/GM-CSFR alpha chimeras revealed that 31 amino acids in the N-terminus of IL-3R alpha were required for MoAb 7G3 binding. MoAb 7G3 may be of clinical significance for antagonizing IL-3 in pathologic conditions such as some myeloid leukemias, follicular B-cell lymphoma, and allergy. Furthermore, these results implicate the N-terminal domain of IL-3R alpha in IL-3 binding. Since this domain is unique to the IL-3/GM-CSF/IL-5 receptor subfamily, it may represent a novel and common binding feature in these receptors.
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PMID:Monoclonal antibody 7G3 recognizes the N-terminal domain of the human interleukin-3 (IL-3) receptor alpha-chain and functions as a specific IL-3 receptor antagonist. 854 80

The ability of total body irradiation (TBI) to eradicate clonogenic leukemia cells from B-lineage acute lymphoblastic leukemia patients prior to bone marrow transplantation (BMT) is greatly hampered by their inherent or acquired radiation resistance. The radiorefractory nature of these cells is believed to contribute to the high relapse rate subsequent to TBI and BMT in patients with B-lineage acute lymphoblastic leukemia (ALL). A method by which clonogenic leukemia cells could be radiosensitized in vivo could be clinically beneficial. In the present study, we used a highly radiation resistant subclone of the murine B-lineage leukemia cell line BCL-1 in a syngeneic BMT model to investigate if any of the B-cell stimulatory cytokines interleukin 2, interleukin 4, interleukin 5, or interleukin 6 could have radiosensitizing effects. All untreated BALB/c mice (N = 33) inoculated with 1 x 10(6) BCL-1 cells died of disseminated leukemia within 24 days with a median survival of 13.3 days. TBI (700 cGy = LD100/30 for BALB/c mice) followed by syngeneic BMT (N = 70) extended the median survival to 23.6 days (P < 0.001 by log-rank test). A single intraperitoneal bolus injection of 100 ng, 500 ng, or 2500 ng recombinant murine interleukin 6(rmIL-6) 2-4 hours before TBI extended the median survival to 32.5 days, 31.0 days, and 30.5 days, respectively (P < 0.01 by log-rank test for all dose groups). The improved survival was not due to any direct anti-leukemic activity of rmIL-6 and all control BALB/c mice (N = 15) that received the same doses of rmIL-6 but did not undergo TBI and BMT died of BCL-1 leukemia within 28 days with a median survival of 13.6 days. In contrast to rmIL-6, recombinant murine interleukin 5 (rmIL-5) had minimal radiosensitizing effects.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:In vivo radiosensitizing effects of recombinant interleukin 6 on radiation resistant BCL-1 B-lineage leukemia cells in a murine syngeneic bone marrow transplant model system. 857 56

A 43-year-old male with newly diagnosed hairy cell leukaemia underwent a single course of 2-chlorodeoxyadenosine (2-CdA). Skin rash, facial swelling and marked eosinophilia developed 20 d after treatment and were resolved by 7 d of steroid therapy. Eosinophil peak in peripheral of the eosinophil population showed a high expression of the IL-2 receptor alpha-chain (CD25), representing up to 94% of gated cells. HLA-DR and CD4 antigens were constantly negative; eosinophils strongly reacted with the secretory form of the eosinophil cationic protein (ECP), recognized by EG2 monoclonal antibody. IL-5 serum levels were markedly elevated at the onset of eosinophilia, returned to normal levels after its disappearance and positively correlated with eosinophil count (r = 0.94, P = 0.016). Eosinophilia is an uncommon finding after treatment with 2-CdA. It is unclear whether these phenomena represented a true allergic reaction to the drug or the effect of massive tumour cell lysis and haemopoietic pancytopenia with immunosuppression, which induced the release of IL-5 and possibly other cytokines.
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PMID:Hypereosinophilia during 2-chlorodeoxyadenosine treatment for hairy cell leukaemia. 860 11

The EoL-1 and EoL-3, human eosinophilic leukemia cell lines, have been used as models for studying the maturation and the function of human eosinophils. We investigated the effects of interferon-gamma (IFN-gamma) on superoxide anion (O2-) production of these cell lines and interleukin-5 (IL-5) mRNA expression in the EoL-1. O2- was measured by chemiluminescence of MCLA, one of cypridina luciferin analogs. The O2- production of fMLP-stimulated EoL-1 and EoL-3 was increased by the IFN-gamma treatment. IL-5 mRNA expression was detected in the IFN-gamma-treated EoL-1 by reverse transcription-polymerase chain reaction (RT-PCR). Further, we examined IFN-gamma receptor 1 mRNA expression in these cell lines and peripheral blood eosinophils by means of northern blot hybridization. IFN-gamma receptor 1 mRNA was detected in the EoL-3 and the IFN-gamma-treated EoL-1. A weak expression of IFN-gamma receptor 1 mRNA was detected in peripheral blood eosinophils isolated from a patient with eosinophilia. These results suggest that IFN-gamma may act on eosinophils directly through its receptor.
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PMID:The direct effect of interferon-gamma on human eosinophilic leukemia cell lines: the induction of interleukin-5 mRNA and the presence of an interferon-gamma receptor. 872 18

Normal T cells secrete cytokines which have important effects on a wide range of other cells. In the present study, the expression of IL-2, IL-4, IL-5, IL-10 and IFN-gamma was assessed in PBMC from 3 cases of T cell leukemia, using reverse transcription and polymerase chain reaction (RT-PCR). The major difference between the leukemia cases and control PBMC samples was that, without in vitro stimulation, IFN-gamma was much more readily detected in 2 of the leukemia cases. IL-2 and IL-5 mRNA were also detected in 2 of the patients but not in the other samples. IL-4 mRNA was not detected in any unstimulated sample, whereas IL-10 was always present. After polyclonal stimulation in vitro, mRNA for all these cytokines was detected in all samples. Thus cytokine expression, particularly of IFN-gamma, may be more prominent in PBMC from adult T cell leukemia cases than in controls.
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PMID:Expression of cytokine genes in T cell leukemias. 877 Nov 54

Interleukin-5 (IL-5), IL-3 and granulocyte-macrophage colony-stimulating factor (GM-CSF) exhibit similar functions on eosinophils, and these common functions are believed to be mediated by the shared beta chain of receptors. IL-5 shows activity on the murine chronic B cell leukemia cell line BCL1-B20, inducing differentiation into IgM-secreting cells, but IL-3 and GM-CSF do not have such activity. To elucidate whether the lineage specificity of IL-5 is due to restricted expression of the IL-5 receptor alpha chain (IL-5R alpha), transfectants of BCL1-B20 were established that express IL-3 receptor alpha (BCL1-3R) or GM-CSF receptor alpha (BCL1-GMR). BCL1-3R and BCL1-GMR acquired responsiveness to IL-3 and GM-CSF, respectively, to an extent similar to IL-5 stimulation, resulting in IgM-secreting cells. Thus, the differentiation of BCL1-B20 into IgM-secreting cells can be equally supported by either IL-3 or GM-CSF, suggesting that intracellular signaling through IL-5R can be replaced by signaling from IL-3R and GM-CSFR. These results support the notion that the lineage specificity of IL-5 is mainly due to the restricted expression of IL-5R alpha. Regulation of IL-5R alpha, IL-3R alpha and GM-CSFR alpha expression in the developmental stage appears to be important for understanding the unique function of these cytokines on a particular cell type.
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PMID:Interleukin-3 (IL-3) and granulocyte-macrophage colony-stimulating factor (GM-CSF) can induce differentiation of chronic B cell leukemia expressing the alpha subunit of IL-3 and GM-CSF receptor. 890 4

Interleukin-5 (IL-5) is produced by T lymphocytes and known to support B cell growth and eosinophilic differentiation of the progenitor cells. Using ATL-16T cells which express IL-5 mRNA, we have identified a region, within the human IL-5 gene promoter, that regulates IL-5 gene transcription. This cis-acting sequence contains the core binding motif, (A/T)GATA(A/G), for GATA-binding family proteins and thus suggests the involvement of these family members. In this report, we describe the cloning of human GATA-4 (hGATA-4) and show that hGATA-4 selectively interacts with the -70 GATA site within the IL-5 proximal promoter region. By promoter deletion and mutation analyses, we established this region as a positive regulatory element. Cotransfection experiments revealed that both hGATA-4 and PMA/A23187 stimulation are necessary for the IL-5 promoter activation. The requirement of another regulatory element called CLE0, which lies downstream of the -70 GATA site, was also demonstrated. ATL-16T cells express mRNA of three GATA-binding proteins, hGATA-2, hGATA-3 and hGATA-4, and each of them has a potential to bind to the consensus (A/T)GATA(G/ A) motif. However, using ATL-16T nuclear extract, we demonstrated that GATA-4 is the only GATA-binding protein that forms specific DNA-protein complex with the -70 GATA site. The electrophoretic mobility shift assay with extracts of COS cells expressing GATA-binding proteins showed that GATA-4 has the highest binding affinity to the -70 GATA site among the three GATA-binding proteins. When the transactivation ability was compared among the three, GATA-4 showed the highest activity. These results demonstrate the selective role of GATA-4 in the transcriptional regulation of the IL-5 gene in a circumstance where multiple members of the GATA-binding proteins are expressed.
Leukemia 1997 Apr
PMID:Of the GATA-binding proteins, only GATA-4 selectively regulates the human IL-5 gene promoter in IL-5 producing cells which express multiple GATA-binding proteins. 920 38


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