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

TCRalphabeta CTL clones recognizing mouse thymus leukemia (TL) Ags were established and categorized into two groups: those killing any TL+ target cells (type I) and those killing only TL+ Con A blasts (type II). Cold target inhibition assays showed that the antigenic determinant(s) recognized by type II clones are expressed not only on TL+ Con A blasts but also on other TL+ target cells. The relation of the target specificity to the killing machinery and the accessory molecules involved in cytotoxicity were therefore analyzed using four representative clones selected from each type. Of the target cells tested, Fas was only expressed on Con A blasts, indicating that Fas ligand (FasL)-dependent cytotoxicity is limited to such cells. All four type II and one of four type I clones expressed FasL on the surface, while both types contained perforin in the cytoplasm. Blocking studies using neutralizing anti-FasL mAbs and concanamycin A (CMA), a selective inhibitor of the perforin pathway, suggested that type I clones kill target cells by way of perforin, while type II clones kill TL+ Con A blasts through FasL together with perforin. For their cytotoxicity, type I CTLs require a signal through CD8, while type II require LFA-1/ICAM-1 interactions. Type II clones also need a co-stimulatory signal through an unknown molecule for perforin-dependent cytotoxicity. These results taken together suggest that the difference in the target specificity of anti-TL CTL clones is due to variation in the killing machineries and the dependence on accessory molecules.
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PMID:Two types of anti-TL (thymus leukemia) CTL clones with distinct target specificities: differences in cytotoxic mechanisms and accessory molecule requirements. 960 21

The biphenotypic cell line BW-90 was established from the peripheral blood of a a patient with a refractory acute myelomonocytic leukemia. All cells were HLADr+, CD34-. Dual color flow cytometry showed simultaneous expression of myeloid (CD33) and B-lymphoid surface markers (CD19) on 60% of cells, CD54 on 91% of cells. Lymphoid lineage markers included CD20/CD22 coexpressed on 89% of cells, CD71 (70%), CD11a (48%), CD18 (54%), and surface lambda light chain (33%). Exposure to various cytokines individually and in combination for up to 14 days had no effect on cell proliferation or differentiation. Only long-term (10-14 days) exposure to 5637 cell-conditioned medium (CCM) induced growth inhibition and differentiation along the monocytic pathway. Differentiation-inducing agents retinoic acid (RA), dimethyl sulfoxide (DMSO) and phorbol 12-myristate 13-acetate (PMA) did not induce differentiation. Differentiation into the monocytic pathway was induced by 5-azacytidine (5AzaC) alone or in combination with verapamil (VP). The BW-90 cell line may serve as a model to study early steps of leukemogenesis and early hematopoiesis. It may provide insight leading to development of an effective therapy for treatment-resistant biphenotypic leukemias.
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PMID:Azacytidine plus verapamil induces the differentiation of a newly characterized biphenotypic human myeloid-B lymphoid leukemic cell line BW-90. 968 94

In order to scrutinize the adherence-dependent interactions for induction of granulocyte colony-stimulating factor (G-CSF) in peripheral monocytes/macrophages, a sensitive reporter gene assay was constructed using the mouse macrophage cell line transfected with the mouse G-CSF promoter region in conjunction with the luciferase gene as a reporter. With this system, lipopolysaccharide (LPS) showed a markedly positive response. Among the extracellular matrix (ECM) proteins, both fibronectin (FN) and vitronectin (VN) markedly induced luciferase activity, but others did so but much lesser extent. Among the synthetic peptides having Arg-Gly-Asp (RGD) sequences, only FLEPP with multiple RGD significantly induced luciferase activity. Pretreatment of the cells with anti-integrin alpha 6, alpha M, beta 1 and beta 2 monoclonal antibodies (mAbs) significantly reduced the LPS-induced responses and anti-alpha 1, alpha 2 and beta 3 mAbs to lesser extent, and anti-alpha 5, alpha 6, alpha M, beta 1 and beta 2 mAbs blocked the FN-induced response. In the cell-to-cell interactions, significantly positive increase was observed by direct contacting this cell line with a G-CSF-dependent promyelocytic leukaemia cell line, known to stimulate the induction of G-CSF to the stromal cells. Its effect was mostly blocked by pretreatment with anti-integrin alpha 5, alpha L, beta 1 and beta 2 and anti-ICAM-1 mAbs. These results indicate that there are several pathways via the cell-to-ECM and cell-to-cell interactions triggering the induction of G-CSF in the macrophages.
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PMID:Stimulation of G-CSF gene expression in the macrophage cell line by contact with extracellular matrix proteins and a pre-B leukaemia cell line. 972 32

We examined the expression of co-stimulatory molecules on leukaemic cells of 52 adult patients with acute myeloid leukaemia (AML) (34 men and 18 women) and analysed the relationship between these expressions and the patient's prognosis. B7-1 was not expressed in any of the 23 patients investigated, whereas B7-2 was expressed in 26/52 patients (50.0%). B7-2 was expressed in all AML patients with monocytic morphology (M4 or M5) and in 16/42 cases without monocytic morphology. CD54 was expressed in 28/ 37 patients examined (75.7%), and CD58 was expressed in all of the AML patients except one (M 7). The overall survival of the 26 B7-2-positive leukaemia patients (1-24 months, median survival 11.5 months) was significantly shorter than that of the 26 B7-2-negative leukaemia patients (1-71+ months, median 35.1 months) (P=0.0080). In addition, the B7-2-positive patients exhibited significantly shorter disease-free survival periods compared to the B7-2-negative patients (P=0.021). There was no significant difference in age, sex, haematological data and complete remission rate between the B7-2-positive and B7-2-negative patients. Our results indicated that B7-2 is one of the most crucial factors in the prognosis of adult acute leukaemia and can be expected to have an important role in tumour immunity.
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PMID:The expression of co-stimulatory molecules and their relationship to the prognosis of human acute myeloid leukaemia: poor prognosis of B7-2-positive leukaemia. 975 54

SR-91 is a natural killer (NK)-resistant leukemic cell line expressing a low level of ICAM-1. Pre-treatment of SR-91 cells with TNF-alpha or IFN-gamma, increased both ICAM-1 (CD54) expression on SR-91 cells and binding to the human NK cell line NK-92. However, only TNF-alpha-treated SR-91 cells became sensitive to killing by NK-92 cells. The increased binding induced by both cytokines and the TNF-alpha-induced sensitivity of SR-91 cells to NK-92 cell killing were abrogated by anti-LFA-1 mAb as well as by a combination of antibodies against the three ligands of LFA-1 (CD11a/CD18), ICAM-1 (CD54), ICAM-2 (CD102) and ICAM-3 (CD50). This indicated that LFA-1 interaction with the three ICAMs on SR-91 cells is essential for effector-target cell binding (which is a prerequisite for subsequent target cell lysis), but is insufficient to render the SR-91 cells sensitive to killing by NK-92 cells. TNF-alpha, but not IFN-gamma also induced the activation of LFA-1, CD44 and beta1 integrins on SR-91 cells. Based on these observations we propose that the differential effect of TNF-alpha and IFN-gamma could be related to the activation of certain adhesion molecules on the surface of SR-91 cells by TNF-alpha that, upon interaction with their counter-receptors on NK-92 cells, lead to the activation of the NK-92 cells.
Leukemia 1998 Oct
PMID:Induction of sensitivity to NK-mediated cytotoxicity by TNF-alpha treatment: possible role of ICAM-3 and CD44. 976 1

Tumor cell lines are generally killed by lymphokine-activated killer (LAK) cells. In this study, however, we report a LAK-resistant cell line, OKM-2T. The OKM-2T is an adult T-cell leukemia (ATL) cell line, and was compared to other ATL cell lines and non-ATL cell lines. The LAK cells were generated from healthy volunteers. Cell surface markers were determined by a flow cytometry test. The ATL and non-ATL cell lines were killed by the LAK cells, markedly or moderately. However, the OKM-2T was scarcely killed. The adhesion tendency of the OKM-2T to the LAK cells was preserved at the same level as that of the other cell lines, whereas the OKM-2T showed low levels of adhesion molecules CD58 (LFA-3), CD86, and CD106 (VCAM-1). We determined blocking tests using specific antibodies. Anti-CD58 blocked the LAK lysis. Anti-CD54 and anti-CD106 enhanced the blocking effect of the anti-CD58; anti-CD86 did not show such an effect. These results suggest that the low expression of CD58 in the OKM-2T may have an intimate relationship with LAK resistance, and that the low expression of CD106 may also be responsible for it, in part.
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PMID:A lymphokine-activated killer (LAK)-resistant cell line, and low expression of adhesion molecules LFA-3 and VCAM-1 on its cell surface. 980 61

Caveolae are plasma membrane invaginations that function as a center for signal transduction. Recent studies indicate that caveolins, the main proteins in caveolae, serve as scaffolding proteins onto which many classes of signaling molecules are assembled. There are multiple forms of caveolins: caveolin-1 and caveolin-2 are expressed as stable heterooligomeric complexes within most cell types, while caveolin-3 is restricted to striated muscle cells. However, neither caveolin proteins nor caveolae structures are detected in peripheral blood cells or blood cell lines. We identified caveolin-1 in one T cell leukemia cell line, a subline of Jurkat cells, by immunostaining and Western blotting. The cells showed enlarged cell bodies similar to activated T cells. This led us to investigate caveolin expression in adult T cell leukemia (ATL) cell lines, which are known to be constitutively activated. Two of five ATL cell lines expressed caveolin-1. The phenotype of caveolin-1-positive cells expressed not only high levels of the T cell activation markers, as with CD25 or HLA-DR, but also CD54 at extremely high levels. These findings demonstrate for the first time that hematological cells express caveolin-1 in certain states of cell activation. In addition, the caveolin-1 expression may be a useful marker for the diagnosis of ATL malignancy.
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PMID:Expression of caveolin-1 in human T cell leukemia cell lines. 987 46

In order to elucidate the possibility of costimulatory molecules-mediated immuno or immuno-gene therapy for human hematological malignancies, we analyzed 30 hematopoietic cell lines and cells obtained from 48 patients with hematological malignancies for the expression of costimulatory molecules such as CD80 and CD86. The 30 hematopoietic cell lines were composed of 4 cell lines derived from the patients with T-cell acute lymphoblastic leukemia (T-ALL), 3 from Philadelphia chromosome positive ALL (Ph1+ALL), 8 from acute myeloblastic leukemia (AML), 3 from acute promyelocytic leukemia (APL), 8 from chronic myeloid leukemia at blast crisis (CML-BC), 3 from Burkitt's lymphoma and one from follicular cell lymphoma. The expression of CD80 or CD86 was frequent on cell lines derived from the patients with CML-BC or Burkitt's lymphoma, while it was rare on cell lines from T-ALL. Subsequently we analyzed the cells obtained from 48 patients with hematological malignancies, which consisted of 6 samples from patients with ALL, 30 from AML, 2 from CML-BC, 3 from B-cell lymphoma and one from each acute mixed leukemia (AMixL), adult T cell leukemia (ATL), T-cell large granular lymphocytic leukemia (T-LGL leukemia), chronic lymphocytic leukemia (CLL), myelodysplastic syndrome (MDS)-RAEB in T, multiple myeloma (MM) or T-cell lymphoma. Among all the 48 cases, all cases except one case with CLL and two with B cell lymphoma were demonstrated to be negative for CD80 on the neoplastic cells. CD86 and HLA-DR were shown to be expressed in 50% and 88% of total 48 cases respectively. In 30 AML samples, CD86 was positive in 15 cases (50%), which was sharply in contrast with the finding that CD80 was not detected in any AML samples. HLA-DR was expressed in 25 AML samples (83%). We also treated seven human hematopoietic cell lines with IFN-gamma, IL-12 or IL-15 and observed whether these cytokines could induce or enhance the expression of CD40, CD54, CD58 and HLA-DR as well as CD80 and CD86. The present study demonstrated that the expression of CD86 could be upregulated not only by IFN-gamma, but also by IL-12 or IL-15 in some cell lines. These findings suggested the possibility that the absence of CD80 on neoplastic cells may be associated with the lack of efficient anti-tumor immunity in most patients with hematological malignancies and that the immuno or immuno-gene therapy manipulating the expression of costimulatory molecules such as CD80 may be a useful treatment modality for hematological malignancies.
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PMID:Expression patterns of costimulatory molecules on cells derived from human hematological malignancies. 989 58

We have previously reported that leukemic dendritic cells (DC) can be generated ex vivo from myelomonocytic precursors in chronic myelogenous leukemia. In this study we report the generation of DC from acute myelogenous leukemia (AML) cells and their potent ability to stimulate leukemia-specific cytolytic activity in autologous lymphocytes. DC were generated in vitro using granulocyte-macrophage colony-stimulating factor +interleukin-4 in combination with either tumor necrosis factor-alpha or CD40 ligand (CD40L). Cells from 19 AML patients with a variety of chromosomal abnormalities were studied for their ability to generate DC. In all but 1 case, cells with the morphology, phenotypic characteristics, and T-cell stimulatory properties of DC could be generated. These cells expressed high levels of major histocompatibility complex class I and class II antigens as well as the costimulatory molecules B7-2 and ICAM-1. In three cases these cells were determined to be of leukemic origin by fluorescence in situ hybridization for chromosomal abnormalities or Western blotting for the inv(16) fusion gene product. Autologous lymphocytes cocultured with AML-derived DC (DC-AL) were able to lyse autologous leukemia targets, whereas little cytotoxicity was noted against autologous, normal cells obtained from the patients during remission. We conclude that leukemia derived DC may be useful for immunotherapy of many AML patients.
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PMID:Dendritic cells derived in vitro from acute myelogenous leukemia cells stimulate autologous, antileukemic T-cell responses. 992 Aug 26

Leukemic T-LGL (large granular lymphocyte) composed of clonal CD3+ TCR alphabeta+ CD8+ CD57+ cells were compared with oligoclonally CD3+ CD8hi+ CD57- lymphocytes expanded after BMT. Leukemic CD3+ CD8hi+ CD57+ LGL showed several phenotypic differences such as an upregulation of CD16 and adhesion molecules (mainly CD11c, CD58 and CD54), activation markers and an exclusive CD45RA isoform expression. Unstimulated CD3+ CD8+ CD57+ LGL from both leukemic and BMT donors spontaneously developed an ex vivo CTL-like CD3-redirected cytotoxicity but no NK cell activity. Different stimuli (PHA, PMA or rhIL-2) induced similar cytotoxic profiles after a 6-day culture involving a CD3-redirected lysis predominating over a low NK cell activity. However, culture of leukemic LGL with these stimuli allowed either a 2 week persistence (PMA or rhIL-2) of CD8+ CD57+ LGL or their disappearance after 3 days (PHA). Furthermore, leukemic CD8hi+ CD57+ T lymphocytes produced an inhibitor of cytotoxic functions as previously described for BMT recipients' CD8+ CD57+ cells. Thus, despite some phenotypic differences between both cell sources, leukemic CD57+ T-LGL display the same functional characteristics of cytotoxic effector and immunoregulatory T cells as CD8+ CD57+ T cells from BMT recipients which might represent their normal counterpart.
Leukemia 1999 Feb
PMID:Leukemic CD3+ LGL share functional properties with their CD8+ CD57+ cell counterpart expanded after BMT. 1002 97


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