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)

Peripheral blood mononuclear cells (PBMC) from 42 patients with acute myelogenous leukaemia (AML) in complete remission (CR) and from normal donors were activated into LAK cells in the presence of 1000 U/ml of recombinant interleukin-2 (rIL-2). Cytotoxicity of LAK cells was assayed against K562, Daudi, and Raji cell lines, and autologous and/or allogeneic thawed leukaemic blasts. Fresh unactivated PBMC from normal donors and AML patients served as controls. Mean +/- standard deviation (SD) percentage lysis of the different targets by patient LAK cells were: K562 61 +/- 20%, Daudi 62 +/- 23%, Raji 48 +/- 24%, autologous blast cells 12 +/- 16% and allogeneic blast cells 13 +/- 10%. Lysis of the different targets by LAK cells from normal donors was similar to that achieved with LAK cells from AML patients. Overall there was a good correlation between the lysis of the different targets. There was no significant difference between the percentage lysis of autologous and allogeneic thawed blast cells, although LAK cells from seven out of the 18 patients tested were unable to lyse autologous leukaemic cells. Activity of patient LAK cells did not correlate with the initial characteristics of the patient nor with the time spent in CR before harvesting PBMC for activation. At the time of analysis, 32 patients were in continuing CR and 10 had relapsed. Multivariant analysis for prognostic factors showed that patients whose LAK cells had more lytic activity on K562 (P = 0.005) and fresh blast cell (P = 0.02) targets had significantly less risk of relapse than patients with little inducible LAK cell activity.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Inducibility of lymphokine activated killer (LAK) cells in patients with acute myelogenous leukaemia in complete remission and its clinical relevance. 201 57

The nuclear protein p53 has been reported to be associated with cell transformation and/or proliferation so that the study of p53 expression in human malignancy has potentially important clinical implications. We have analyzed the p53 expression in mitogen-stimulated and nonstimulated human lymphocytes, in several human leukemia cell lines (Molt-4, Raji, Daudi, HL-60, KG-1, K562 and U937) and in fresh bone marrow (BM) cells. Simultaneous differential staining of p53 (identified by a FITC-labeled monoclonal antibody) versus DNA (stained with propidium iodide, PI), followed by bivariate analysis with flow cytometry (FCM) made it possible to evaluate p53 expression with respect to cell position during the cell cycle. The data show that in stimulated lymphocytes p53 is progressively accumulated during the G1, S and G2-phases, while in non-stimulated conditions most cells are remaining in G0/G1 and express p53 to a lesser degree. This suggests that expression of p53 is more correlated with cell growth than with entrance into (or progression through particular phases of) the cell cycle. Cells from acute lymphoblastic leukemia (ALL) and Burkitt's lymphoma cell lines express elevated levels of p53, while all examined human acute myeloid leukemia cell lines synthesize negligible p53 protein. Understanding the variations in p53 expression in different types of human leukemia may provide some insight into the biologic roles of p53 in normal and malignant cells.
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PMID:Expression of p53 protein during the cell cycle measured by flow cytometry in human leukemia. 214 May 91

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

A murine monoclonal antibody has been produced which identifies a novel human leucocyte differentiation antigen. The antibody, designated WM-66, of IgM subclass, was cytolytic with human complement. WM-66 was shown to react with virtually all normal T and B lymphocytes from peripheral blood and lymphoid tissues, as well as blood monocytes and approximately 40% of bone marrow mononuclear cells. The antibody also bound to the majority of cases of chronic B-cell malignancies, including chronic lymphatic leukaemia and non-Hodgkin's lymphoma, but not to cases of acute leukaemia or to the majority of leukaemic and lymphoblastoid cell lines. WM-66 also reacted with epithelium of bronchus and salivary gland ducts. A single band of relative molecular mass 65,000 Daltons was immunoprecipitated from membrane extracts of normal lymphocytes and the B-cell line Daudi. Treatment of a number of WM-66-negative B-cell lines with neuraminidase resulted in WM-66 binding, indicating that the antigen exists in a covert form masked by sialic acid residues on a wider spectrum of cell types than was initially apparent. The reactivity pattern of WM-66 indicates that it recognises a previously undescribed surface membrane molecule with broad non-lineage-specific distribution on leucocytes. This has recently been confirmed at the Fourth International Workshop on Human Leucocyte Differentiation Antigens. Although the biological function of the molecule recognised by WM-66 is unknown, the lytic properties of the antibody suggest a possible in vivo therapeutic role as an immunosuppressant or for treatment of lymphoid malignancy.
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PMID:A novel human leucocyte surface membrane antigen defined by murine monoclonal antibody. 224 85

A cDNA clone encoding the human lymphocyte differentiation Ag CD38 was isolated from a mixture of four different lymphocyte CDNA libraries expressed transiently in COS cells and screened by panning with mAb. Transfected COS cells expressed a surface protein of Mr 46,000 that was similar to the native CD38 molecule expressed on the B cell line Daudi and the T cell leukemia HPB-ALL and which was recognized by each of the CD38 specific mAb HIT-2, T16, T168, HB7, 5D2, ICO-18, and ICO-20. The CD38 cDNA sequence predicts an unusual 30-kDa polypeptide with a short N-terminal cytoplasmic tail, and a carboxyl-terminal extracellular domain carrying the four potential N-linked glycosylation sites. The absence of significant homology with other known surface Ag including members of the Ig superfamily ruled out the possibility that CD38 was the human homologue of the murine Qa2 molecule as has been suggested previously. PvuII digests of human genomic DNA revealed a polymorphism linked to the CD38 gene.
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PMID:Isolation of a cDNA encoding the human CD38 (T10) molecule, a cell surface glycoprotein with an unusual discontinuous pattern of expression during lymphocyte differentiation. 231 35

Several lines of evidence are compatible with the hypothesis that Epstein-Barr virus (EBV) nuclear antigen 2 (EBNA-2) or leader protein (EBNA-LP) affects expression of the EBV latent infection membrane protein LMP1. We now demonstrate the following. (i) Acute transfection and expression of EBNA-2 under control of simian virus 40 or Moloney murine leukemia virus promoters resulted in increased LMP1 expression in P3HR-1-infected Burkitt's lymphoma cells and the P3HR-1 or Daudi cell line. (ii) Transfection and expression of EBNA-LP alone had no effect on LMP1 expression and did not act synergistically with EBNA-2 to affect LMP1 expression. (iii) LMP1 expression in Daudi and P3HR-1-infected cells was controlled at the mRNA level, and EBNA-2 expression in Daudi cells increased LMP1 mRNA. (iv) No other EBV genes were required for EBNA-2 transactivation of LMP1 since cotransfection of recombinant EBNA-2 expression vectors and genomic LMP1 DNA fragments enhanced LMP1 expression in the EBV-negative B-lymphoma cell lines BJAB, Louckes, and BL30. (v) An EBNA-2-responsive element was found within the -512 to +40 LMP1 DNA since this DNA linked to a chloramphenicol acetyltransferase reporter gene was transactivated by cotransfection with an EBNA-2 expression vector. (vi) The EBV type 2 EBNA-2 transactivated LMP1 as well as the EBV type 1 EBNA-2. (vii) Two deletions within the EBNA-2 gene which rendered EBV transformation incompetent did not transactivate LMP1, whereas a transformation-competent EBNA-2 deletion mutant did transactivate LMP1. LMP1 is a potent effector of B-lymphocyte activation and can act synergistically with EBNA-2 to induce cellular CD23 gene expression. Thus, EBNA-2 transactivation of LMP1 amplifies the biological impact of EBNA-2 and underscores its central role in EBV-induced growth transformation.
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PMID:Epstein-Barr virus nuclear antigen 2 transactivates latent membrane protein LMP1. 235 28

The authors have developed a panel of monoclonal antibodies (MCA) of IPO series (Institute of Problems of Oncology, Kiev). RPMI-1788 cell line, Daudi, as well as splenocytes of a patient with hairy-cell leukemia were used for immunization of mice. It has been shown that IPO-3, IPO-10 and IPO-24 MCA are directed against differentiation antigens of human B-lymphocytes. IPO-4 MCA reveal the antigen of activated T- and B-cells. IPO-5 and IPO-20 MCA recognize HLA-ABC, while IPO-37 a common leucocytic antigen. IPO-38 MCA are directed against the nuclear antigen. The possibilities of using IPO MCA in hematology have been discussed.
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PMID:[Monoclonal antibodies of the IPO series in studying and diagnosing malignant lymphoproliferative diseases]. 237 43

Three murine monoclonal antibodies, named 2H9, 1E9 and 1A2, were produced after immunization of BALB/c mice with cells of the SU-DHL-1 cell line from a true histiocytic lymphoma. In frozen sections from various lymphomas, 2H9 and 1A2 selectively stained the cell membranes of neoplastic cells in true histiocytic lymphoma and Hodgkin's disease. Antibody 1E9 stained the nuclear membranes of the tumor cells in true histiocytic lymphoma and malignant histiocytosis. No staining was seen in 56 cases of B and T cell lymphoma. Several tissue culture cell lines, including T cell acute lymphoblastic leukemia and pre-B cell lines, were not stained. With 2H9, however, a positive reaction was noted for two Epstein-Barr virus (EBV)-positive African Burkitt's lymphoma cell lines (Daudi and P3HRI), one human T cell lymphoma/leukemia-virus-positive cell line (HUT 102), and one EBV-transformed normal B lymphoblastoid cell line (RPMI 8057). In normal lymphoid tissues, 2H9 and 1E9 reacted with the nuclear membranes of histiocytes and interdigitating reticulum cells, whereas 1A2 stained only rare cells of an unknown type. All three antibodies failed to react with B or T cells in frozen tissue sections of normal lymphoid tissues. The use of these three antibodies should facilitate the diagnosis of histiocyte and interdigitating reticulum (IR) cell-related neoplasms, namely, true histiocytic lymphoma, malignant histiocytosis, and Hodgkin's disease. True histiocytic lymphoma and Hodgkin's disease exhibit similar reactivities with these three and with two other monoclonal antibodies (HeFi-1 and Tac), suggesting that these two types of lymphoma are related. In contrast, malignant histiocytosis was negative for 2H9, 1A2, Tac, and HeFi-1. The difference in the phenotypic expression of true histiocytic lymphoma and malignant histiocytosis indicates that they are two different disease entities.
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PMID:Monoclonal antibodies against SU-DHL-1 cells stain the neoplastic cells in true histiocytic lymphoma, malignant histiocytosis, and Hodgkin's disease. 242 24

It is known that IL-2 induces lymphocytes to produce interferon-gamma (IFN-gamma) and this IFN type is particularly efficient in inducing tumor cell resistance to natural killer (NK) cell-mediated lysis. We have investigated the effect of IFN on tumor cell sensitivity to LAK cell-mediated cytotoxicity. Pretreatment of the human K562 leukemia and HHMS melanoma with IFN-gamma and the Daudi lymphoma with IFN-alpha caused a significant reduction in sensitivity to lysis by human LAK cells generated in vitro in the presence of human recombinant IL-2 (100 U/ml). The LAK activity was mediated by cells expressing NK cell markers (CD16,NKH1) as well as by cells with T cell markers (CD3, CD5). IFN-treated K562 cells were protected from lysis mediated by all these populations. Supernatants from LAK cultures containing IFN-gamma were able to induce NK and LAK resistance when used to pretreat K562 overnight. Antibodies to IFN-gamma but not to IFN-alpha were able to neutralize this activity. Taken together, these results indicate that the production of IFN-gamma by LAK cells may be of importance in induction of tumor cell resistance to LAK cell-mediated lysis.
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PMID:Interferon is able to reduce tumor cell susceptibility to human lymphokine-activated killer (LAK) cells. 246 94

This study was conducted to assess the enhanced antitumor effects of natural human tumor necrosis factor alpha (nHuTNF-alpha) and natural human interferon alpha or gamma (nHuIFN-alpha or -gamma), in combination, on ten human cancer cell lines. The cell lines tested were colon cancer (RPMI4788), lung cancer (PC10), gastric cancer (MKN-1 and MKN-28), nasopharyngeal cancer (KB), leukemia (K562), lymphoma (Daudi), Liver cancer (H-7) and breast cancer (ZR-75-30 and ZR-75-1). A mixture of nHuTNF-alpha and nHuIFN-alpha (1:1, by unit) showed cytotoxic effects on nHuTNF-alpha resistant cell lines such as RPMI4788, KB and Daudi or nHuIFN-alpha resistant cell lines such as KB, and ZR-75-1, as well as on nHuTNF-alpha or nHuIFN-alpha sensitive cells. A synergistic antitumor effect occurred in four cell lines (RPMI4788, PC10, Daudi and ZR-75-1) treated with a combination of nHuTNF-alpha and nHuIFN-alpha. Also, a combined treatment with nHuTNF-alpha and nHuIFN-gamma (1:1/100, by unit) showed cytotoxic effects on nHuTNF-alpha or nHuIFN-gamma resistant cell lines such as MKN-1, MKN-28, Daudi, H-7 and ZR-75-1. A synergistic antitumor effect occurred in eight cell lines (RPMI4788, PC10, MKN-1, MKN-28, KB, Daudi, H-7 and ZR-75-1). Thus, the combined treatment with nHuTNF-alpha and nHuIFN-alpha or -gamma expanded the spectrum of sensitive cells. These results indicate that the combined use of nHuTNF and nHuIFN may provide a certain approach to cancer treatment.
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PMID:Synergistic antitumor effects of natural human tumor necrosis factor-alpha and natural human interferon-alpha or -gamma on human cancer cell lines. 250 39


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