Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0023418 (leukemia)
 93,477 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

To help understand host-tumor relationships in adult acute lymphoblastic leukemia (ALL) and to better define potential indications for interleukin-2 (IL-2) treatment in this disease, the relationship between the susceptibility of leukemia cells of 22 patients with ALL to lysis by allogeneic lymphokine-activated killer (LAK) cells and characteristics of the leukemia was studied. Lymphocytes were activated in the presence of 1000 U/ml recombinant IL-2 for 5 days. The lysis of ALL cells was studied by the release of 51Cr. The average lysis of ALL cells by control, unactivated lymphocytes was 1.2 +/- 2.4% and by LAK cells 8.9 +/- 8.6%. The susceptibility of leukemic cells to lysis did not correlate with the expression of lymphoid or myeloid differentiation markers or expression of the adhesion molecules CD54 (ICAM-1) and CD58 (LFA-3). Leukemic cells of the FAB I2 subtype were significantly more resistant to lysis than those of the other subtypes (average lysis 1.4 +/- 3.0% versus 12.3 +/- 8.2%, p = 0.003). The susceptibility to lysis did not correlate with the other initial characteristics of the leukemia. The 11 patients in whom 8% or more of leukemic cells were lysed by allogeneic LAK cells survived significantly longer than the 11 patients whose blast cells were less susceptible to lysis (p = 0.04). It is concluded that IL-2 treatment might be of benefit in adult ALL, particularly in non-L2 FAB subtypes and during complete remission to possibly delay relapse and prolong survival.
Leukemia 1991 Nov
PMID:Susceptibility of adult acute lymphoblastic leukemia blasts to lysis by lymphokine-activated killer cells. 196 Oct 38

In order to clarify the function of human S100 beta-positive T-cells, S100 beta-positive T-leukemia cells (S100 beta TLC) were examined in vitro. S100 beta TLC were obtained from the peripheral blood of a patient with S100 beta-positive T-cell leukemia and enriched by an E-rosetting method. Two dimensional flow cytometric analysis indicated that the vast majority of the E-positive fraction were S100 beta TLC expressing CD3 and CD8 antigens. Although S100 beta TLC expressed CD3 antigen, they were negative for the alpha/beta and gamma/delta T-cell antigen receptor (TCR) defined by monoclonal antibodies (mabs) WT-31 and delta TCS-1, respectively. It was speculated that S100 beta TLC initially expressed alpha/beta TCR but lost it during malignant transformation. When S100 beta TLC were cultured for 24 h, they acquired cytotoxic activity towards various NK-sensitive cell lines including K-562, Molt-3 and CEM-CCLF, but did not exhibit lysing activity towards NK-resistant cell lines including Raji, Daudi and MT-1. Despite the NK-activity of cultured S100 beta TLC, they lacked the morphological features of large granular lymphocytes (LGL). S100 beta TLC did not exhibit lymphokine-activated killer (LAK) activity. When S100 beta TLC were cocultivated with NK-sensitive cells or NK-resistant cells, they selectively bound to NK-sensitive cells, indicating that they lysed target cells by cell-to-cell contact. The finding that S100 beta TLC lacked TCR molecules and their NK activity was not inhibited by mabs reactive with the CD3-TCR complex indicated that the CD3-TCR complex was not involved in their target recognition.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Natural killer (NK) activity of cultured S100 beta-positive T-leukemia cells. 198 Jul 62

Adherent lymphokine activated killer (ALAK) cells are a subpopulation of activated natural killer (NK) cells with MHC unrestricted antitumour activity distinguished by their propensity to adhere to plastic in the presence of interleukin-2 (IL-2). We generated ALAK cells from seven patients with chronic myeloid leukaemia (CML) following Campath-1-depleted bone marrow transplantation (BMT). Five had relapsed and were in chronic phase, one had cytogenetic evidence of relapse and one had prior evidence of cytogenetic relapse but was in complete remission at time of study. Phenotypically the ALAK cells included both CD56+/CD3- NK cells and CD56-/CD3+ T cells. The CD3- subpopulation were studied cytogenetically and their functional activity tested in a 4 h 51Cr release cytotoxicity assay using the pretransplant leukaemia cells as targets. Cytogenetic studies showed that the ALAK cells from six patients were Ph negative, and where donor and recipient were sex mismatched, ALAK cells were exclusively of donor origin. In one patient ALAK cells were Ph positive and of recipient origin in eight of nine metaphases. In the 51Cr release assay the ALAK cells showed significant lysis of the pretransplant leukaemia in five of the seven patients tested. These data indicate that in CML patients who relapse post-BMT the NK cells are usually of donor origin but may be recipient-derived. In most patients these ALAK cells have antileukaemic activity in vitro.
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PMID:Origin and function of adherent lymphokine activated killer cells in patients with chronic myeloid leukaemia who relapse following bone marrow transplantation. 199 98

Natural antibodies (NAb), natural killer (NK) cells and activated macrophages have all been implicated in the rejection of threshold syngeneic tumor inocula. Previous analysis of tumor susceptibility in normal versus inbred and F1 mice bearing the B cell deficiency associated with the xid mutation of CBA/N mice demonstrated an inverse relationship between the tumorigenicity of the RI-28, a radiation-induced leukemia of the CBA/H strain, and the pooled anti-RI-28 serum NAb levels in mice with the same genetic origins. No relationship with tumor susceptibility was seen with NK cell or in vivo activated macrophage cytolysis. Flow-cytometric determination of antitumor serum NAb bled from individual male and female (CBA/N X CBA/J)F1 mice 1 week prior to the threshold tumor inoculation has revealed extensive heterogeneity within the NAb levels of each sex. A comparative analysis of tumor fate with NAb activity revealed that tumors appeared in only 26.3% of animals with a mean fluorescence channel binding above 60 channels in contrast with 77.3% of animals with lower NAb levels. These data extend to the level of individual hosts the support for an inverse relationship between host NAb activity and tumor susceptibility. In addition, subsequent analysis of serum antitumor NAb levels, splenic NK cytolysis and in vitro lymphokine-activated macrophage activity with all three mediators originating from the same individual F1 mice showed no consistent correlations between these natural resistance activities, arguing for the exclusion of deficiencies in NK cell or macrophage function as the basis for the differential tumor susceptibility in individual F1 mice.
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PMID:Inverse correlation between natural antitumor antibodies and tumor susceptibility in individual xid-bearing mice. 205 21

Murine interleukin 5 (IL-5), a lymphokine produced by helper T cells, is involved in the regulation of growth and differentiation of B cells and other hematopoietic cells. The receptor for IL-5 has been identified as two cross-linked complexes on T88-M cells (a murine IL-5-dependent early B cell line). In this study the IL-5 receptor was directly characterized by utilizing an immobilized IL-5 column and a rat monoclonal antibody, designated H7, directed against the IL-5 receptor. H7 completely inhibited specific binding of 35S-labeled IL-5 to T88-M cells, and bound to IL-5-responsive cells, e.g. T88-M, BCL1-B20 (a chronic B-cell leukemia), and MOPC104E (a myeloma), whereas H7 did not bind to IL-5-non-responsive cells, e.g. X5563 (a myeloma), FDC-P1 (an IL-3-dependent line), and MTH (an IL-2-dependent CTLL). H7 could barely bind to T88-M cells in the presence of IL-5, and immunoprecipitated a major band with an Mr of approximately 60 kd from the extract of surface-radioiodinated T88-M cells. The precipitation of this 60 kd molecule was inhibited by the addition of IL-5. Analysis with immobilized IL-5 also revealed that a 60 kd molecule bound specifically to IL-5-coupled beads compared with control beads. Furthermore, no additional molecule with a higher Mr that was recognized by H7 appeared under non-reducing, compared with reducing, conditions. The 60 kd molecule recognized by H7 could be digested with N-glycanase to yield a protein band of approximately 55 kd.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Characterization of the murine interleukin 5 receptor by using a monoclonal antibody. 208 84

Permeablization of human K562 leukemia cells was measured in the presence and absence of extracellular ionic calcium to examine the relationship of ionic calcium to increased membrane permeability and the inhibition of cell proliferation by this lymphokine. In the absence of extracellular calcium, the ability of leukoregulin to permeabilize the cell membrane is diminished but is fully restored by addition of 1 mM extracellular Ca++ as shown flow cytometrically by loss of intracellular fluorescein. Membrane permeability is also increased by calcium ionophore A23187 but permeablization is completely blocked in calcium-free medium despite the intramembrane presence of the calcium ionophore. Membrane permeablization by the lectin phytohemagglutinin, in contrast, is independent of extracellular calcium. A similar divergence in cell proliferation activity of the three modulators of calcium flux and membrane permeability occurs in the absence of extracellular calcium. Leukoregulin inhibition of cell proliferation is abolished, inhibition by calcium ionophore A23817 is greatly reduced, and inhibition by phytohemagglutinin is unchanged. Leukoregulin permeabilized K562 cells isolated by fluorescence activated cell sorting resume proliferation after 72 h. In contrast cells permeablized by calcium ionophore A23187 or phytohemagglutinin fail to resume proliferation by 7 days. The membrane permeablizing action of leukoregulin is, therefore, partially dependent upon extracellular calcium. It is also effected through a mechanism other than calcium ionophore transport or lectin type transmembrane signaling, and is accompanied by a reversible inhibition of cell proliferation.
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PMID:Influence of extracellular calcium on cell permeabilization and growth regulation by the lymphokine leukoregulin. 211 34

We have developed a model system to study immunologically mediated regression of leukemia based on Friend virus-induced erythroleukemias. This system has been used to evaluate the immunotherapeutic activity of macrophages, specifically reactive T-cells (CTL/RFB), lymphokine-activated killer cells and interleukin 2, and tumor necrosis factor alpha and interferon-gamma. In the present studies, CTL/RFB were evaluated for their ability to prevent disease recurrence. Animals with the regressing strain of Friend virus at Day 39 post virus were treated with either one or two injections of 5 x 10(6) CTL/RFB. Animals given one or two injections of CTL/RFB had a significantly lower rate of recurrence than did untreated animals. The helper T-cell component of CTL/RFB was implicated in causing leukemia regression. Interleukin 1 alpha and tumor necrosis factor alpha, multifunctional cytokines with similar biological activities, were evaluated for their ability to suppress leukemic erythroid colony-forming cells and induce regression. Interleukin 1 alpha suppressed the conventional strain of, but not the polycythemia-inducing strain of, Friend virus-leukemic late erythroid colony-forming units and caused only a temporary regression of disease, while tumor necrosis factor alpha suppressed both forms of the disease and with multiple inoculations could cause permanent disease regressions. This system provides an excellent model for examining the efficacy of immunotherapy of leukemias with various mediators and effector mechanisms.
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PMID:Immunotherapeutic approaches to leukemia: the use of the Friend virus-induced erythroleukemia model system. 211 83

Biological modification in cancer therapy involves many different strategies and substances. Bacterial products with established usefulness include BCG, C. parvum and L-Asparaginase. Immunotherapy with such agents has not, however, found general application, although revived interest in 'Coley's mixed toxins' (used earlier this century) paralleled the development of their presumed effector molecules, tumour necrosis factor and lymphotoxin. Many other Cytokines, both natural or recombinant, are now produced on a vast scale following the recent biotechnology revolution. Of these, Alpha Interferons have already proved useful in hairy cell leukaemia, carcinoid tumours, renal cell cancer, Kaposi's sarcoma, chronic granulocytic leukaemia and certain lymphomas, whilst their use as adjuvants or in combination is currently being investigated. More recently, Interleukin-2, which stimulates the clonal expansion of activated T-cells, has shown promise both as a single agent, and when used with lymphokine activated killer (LAK) cells or tumour infiltrating lymphocytes (TILS). A different approach involves the Colony Stimulating Factors such as G-CSF and GM-CSF which reduce the degree and duration of treatment-related myelosuppression, thereby allowing more intensive cytotoxic or radiation therapy, as well as facilitating early recovery following bone marrow transplantation. Monoclonal antibodies have not proved as specific for malignant cells as was originally hoped, but certain tumours, such as lymphoma, are now realistic targets for therapy. Increasingly sophisticated effector mechanisms (e.g. conjugated pro-drugs) and genetically engineered "humanised" monoclonal antibody hybrids present the brightest hopes for the future. Biotherapy, the "fourth modality of cancer treatment" has already assumed its place alongside surgery, radiotherapy and cytotoxic chemotherapy, and will grow in importance as our understanding of the molecular biology of cancer increases in the coming decades.
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PMID:Biological modifiers and their role in cancer therapy. 218 42

Interleukin-2 (IL-2) is a regulator of diverse functions of the immune system that can induce regressions in some experimental and human tumors. These early findings suggest a potential role for IL-2 in the treatment of certain malignant neoplasms including lymphomas and leukemias. Advanced, rapidly growing tumors are generally not amenable to immunotherapy. Therefore, it is more likely that protocols with IL-2 will be used to prolong remission and prevent relapse in leukemia patients with minimal tumor load. Several approaches are currently being tested in animal experiments and clinical trials. Activation of tumor-reactive lymphocytes (specific or nonspecific) by IL-2 in vivo may eradicate residual leukemia in patients with occult disease. In vitro-propagated autologous or allogeneic leukemia-reactive T cells may be infused with IL-2 to facilitate the tumor destruction. The IL-2 enhances monoclonal antibody-dependent effector systems, such as antibody-dependent cell-mediated cytotoxicity in vivo. Monoclonal antibodies recognizing epitopes on leukemia/lymphoma cells could therefore be used with IL-2 to target nonspecific effectors to destroy tumor cells. Other cytokines appear to potentiate various antitumor activities of IL-2, including cytotoxicity of antigen-specific T lymphocytes or lymphokine-activated killer cells in vitro, and these combined effects may be exploited in clinical trials in which more than one cytokine is used simultaneously or in sequence. Finally, a stepwise completion of clinical protocols testing this immunologic approach in combination with other treatment modalities is necessary.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Prospects for interleukin-2 therapy in hematologic malignant neoplasms. 218 78

The human metastatic tumor cell line CAP-2, produces a soluble factor that induces resistance to NK lysis of K-562 susceptible leukemia cell line, and does not inhibit the cytotoxic capacity of effector cells. The use of sequential HPLC, hydrophobic interaction chromatography, and reverse phase chromatography, coupled with cytotoxic assays, resulted in the isolation and separation to homogeneity of a novel protein responsible for this biologic activity. Size estimation studies based on TSK HPLC columns showed that this protein has a mass of 8 to 12 kDa. The amino acid composition analysis of the CAP-2 protein calculated from HPLC chromatograms shows that this protein contains around 108 amino acids. Subsequent gas phase sequence analysis, however, was hampered because the N terminus of this protein was blocked and therefore unsuitable for sequencing by Edman degradation. The functional studies showed that the NK lysis-resistance activity of the CAP-2 protein is mediated by interaction with and nonspecific binding to NK target cells. The lymphokine-activated killer and macrophage-mediated cytotoxicity and mitogen-induced proliferation is not affected. Unexpectedly, the CAP-2 protein appears to be mitogenic to its own cell line. Thus, the induction of NK lysis-resistance and the mitogenic activity showed by CAP-2 protein could contribute to the tumor growth and metastatic establishment.
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PMID:Isolation of a novel tumor protein that induces resistance to natural killer cell lysis. 223 Jan 33


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