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)

The neural cell adhesion molecule (N-CAM/CD56) is a member of the Ig supergene family that has been shown to mediate homophilic binding. Several isoforms of N-CAM have been identified that are expressed preferentially in different tissues and stages of embryonic development. To examine the primary structure of N-CAM expressed in leukocytes, N-CAM cDNA were generated by polymerase chain reaction from RNA isolated from normal human NK cells and the KG1a hematopoietic leukemia cell line. The sequence of leukocyte-derived N-CAM cDNA was essentially identical with N-CAM cDNA from human neuroblastoma cells that encode the 140-kDa isoform of N-CAM. Inasmuch as N-CAM is preferentially expressed on human NK cells and a subset of T lymphocytes that mediate MHC-unrestricted cell-mediated cytotoxicity, we examined the potential role of N-CAM in cell-mediated cytotoxicity and heterotypic lymphocyte-tumor cell adhesion. N-CAM loss mutants were established from the human N-CAM+ KG1a leukemia cell line, and N-CAM cDNA was transfected into a human colon carcinoma cell line and murine L cells. Using this panel of mutants and transfectants, it was determined that expression of N-CAM on these target cells does not affect susceptibility to resting or IL-2-activated NK cell-mediated cytotoxicity. Moreover, expression of N-CAM in these transfectants failed to induce homotypic or heterotypic cellular adhesion. Collectively, these studies indicate that homophilic N-CAM interactions probably do not mediate a major role in the cytolytic interaction between NK cells and N-CAM+ tumor cell targets.
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PMID:Molecular and functional analysis of human natural killer cell-associated neural cell adhesion molecule (N-CAM/CD56). 171 Feb 51

Three predominantly CD8+ CTL lines, TIL 501, TIL 620, and TIL 660, were generated from three HLA-A2+ melanoma patients by culturing tumor-infiltrating lymphocytes in 1000 U/ml IL-2. These tumor-infiltrating lymphocytes lysed 12 of 18 HLA-A2+ autologous and allogeneic melanomas, but none of 20 HLA-A2-negative melanomas. They also did not lyse the MHC class I negative lymphoma-leukemia cell lines, Daudi, K562, or HLA-A2+ non-melanoma cell lines including PHA or Con A-induced lymphoblast, fibroblast, EBV-transformed B cell, Burkitt's B cell lymphoma, and colon cancer cell lines. Autologous and allogeneic melanoma lysis was inhibited by anti-CD3, by anti-MHC class I, and by anti-HLA-A2 mAb, indicating recognition of shared tumor Ag among melanoma cell lines in a TCR-dependent, HLA-A2-restricted manner. Six HLA-A2-negative melanoma cell lines obtained from five HLA-A2-negative patients were co-transfected with the HLA-A2.1 gene and pSV2neo. All 17 cloned transfectants expressing cell surface HLA-A2 molecules, but none of 12 transfectants lacking HLA-A2 expression, were lysed by these three HLA-A2-restricted, melanoma-specific CTL. Lysis of the HLA-A2+ transfectants was inhibited by anti-CD3, by anti-MHC class I, and by anti-HLA-A2 mAb, indicating recognition of shared tumor Ag on transfectants in a TCR-dependent, HLA-A2-restricted manner. These results identify the HLA-A2.1 molecule as an Ag-presenting molecule for melanoma Ag. They also suggest that common melanoma Ag are expressed among melanoma patients regardless of HLA type. These findings have implications for the development of melanoma vaccines that would induce antitumor T cell responses.
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PMID:Shared human melanoma antigens. Recognition by tumor-infiltrating lymphocytes in HLA-A2.1-transfected melanomas. 172 79

Intrathymic inoculation of radiation-leukemia virus (RadLV) into C57BL/6 mice induces a population of pre-leukemic (PL) T cells which progress into clonal, mature thymic lymphomas after a latency period of 3 to 5 months. In order to understand how PL cells are retained in the thymus for a prolonged period of time we determined whether RadLV infected cells secrete and/or respond to a T-cell growth factor that may be involved in the long-term maintenance of a thymic PL-cell pool. We have previously found that in vitro proliferation of RadLV-infected PL cells is IL-4-dependent. Here we show that RadLV induces IL-4 secretion and IL-4 receptor (IL-4R) expression in normal thymic lymphocytes. RadLV-infected PL thymocytes express IL-4R and secrete IL-4. Their IL-4 secretion could be enhanced if incubated in the presence of RadLV and this enhancement was inhibited by anti-RadLV antibodies. Several RadLV-induced lymphoma lines secreted IL-4 and/or expressed IL-4R, but these features were not essential for their continuous growth. The results suggest that RadLV induces IL-4-dependent autocrine growth which maintains a population of PL T cells in the thymus. Transition from a PL state to overt thymic lymphoma involves emancipation of a PL cell from IL-4 dependency.
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PMID:Induction of IL-4 secretion by the radiation leukemia virus (RadLV): role in autocrine growth stimulation of RadLV infected pre-leukemic cells. 173 16

Sera of 15 healthy controls and 33 patients suffering from myelodysplastic syndromes (MDS) were investigated for soluble interleukin-2 receptor (sIL-2R) expression with a cell-free enzyme-linked immunosorbent assay (ELISA) system (T-Cell Sciences; Cambridge, U.S.A.). The upper limit of the assay is indicated with 477 U/ml. According to the FAB classification eight refractory anaemia (RA), 15 refractory anaemia with excess of blasts (RAEB), five refractory anaemia with excess blasts in transformation (RAEBt) and five chronic myelomonocytic leukaemia (CMML) were examined. None of the patients had reported infectious episodes or been under treatment with cytotoxic agents and/or cytokines within the previous 3 months. Significant differences in sIL-2R levels between RA (median 368 U/ml). RAEB (median 675 U/ml) and RAEBt (median 971 U/ml) and between RA and CMML (median 723 U/ml) were detected. Six patients, who had been under treatment with rhGM-CSF for at least 2 weeks, demonstrated a three- to sevenfold increase of sIL-2R expression compared to pretreatment levels. In kinetic evaluation of serum samples for 24 h, the increase of sIL-2R expression begins within 4 h after subcutaneous application of GM-CSF and reaches its maximum after 12 h. Our data cannot suggest whether increased sIL-2R expression is a primary event due to involvement of lymphocytes in the malignant clone or whether it results from secondary alteration of the cytokine network. Application of GM-CSF in MDS may result in improvement of altered lymphocyte function. As GM-CSF induces sIL-2R expression, a down regulation of the immune response caused by neutralization of free IL-2 cannot be excluded.
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PMID:Detection of soluble IL-2 receptor in the serum of patients with myelodysplastic syndromes: induction under therapy with GM-CSF. 175 71

Human interleukin-2 receptor cDNA was transfected into mouse fibroblast cells (L929) by using DNA-calcium phosphate coprecipitation method. Results from RNA dot-blot hybri dization, FITC-IL-2 fluorescent staining assay and anti-Tac specific rossette test demonstrated that the product of human interleukin-2 receptor cDNA in L929 cells is able to bind IL-2 and anti-Tac antibody. Moreover, the abnormal expression of IL-2R gene in T-cell leukemia cell lines such as Jukat cells and Molt-4 cells was analyzed and discussed.
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PMID:[Studies of the expression of human interleukin-2 receptor cDNA in mammalian cells]. 176 Jan 93

We investigated the proliferative effects of interleukins 1-7 (IL-1 to -7) on leukemic cells from 10 patients with T-lineage acute lymphoblastic leukemia (T-ALL). Five patients had CD7+4-8-acute leukemia, one had CD5+ acute leukemia, and four had CD1+ acute leukemia. To examine the proliferative effect of each interleukin, 3H-TdR incorporation method was used. In the presence of IL-1, no increase in 3H-TdR incorporation was observed for any of the T-ALL cells. With IL-2, 3H-TdR incorporation increased in cells from 5 out of 10 T-ALL patients, including those with CD7+4-8-, CD5+, and CD1+ acute leukemia. In the presence of IL-3 or IL-6, 3H-TdR incorporation increased in cells from 2 out of 5 patients with CD7+4-8- acute leukemia. However, CD5+ or CD1+ acute leukemia cells were not stimulated by IL-3 or IL-6. With IL-4, 3H-TdR incorporation was increased in the cells from 2 out of 5 patients with CD7+4-8- acute leukemia and in the cells of 2 of those with CD1+ acute leukemia. IL-5 increased the 3H-TdR incorporation by cells from 2 out of 5 patients with CD7+4-8- acute leukemia and 1 patient with CD1+ acute leukemia. IL-7 increased 3H-TdR incorporation in cells from all five CD7+4-8- acute leukemia and 2 of those with CD5+ or CD1+ leukemia. No synergistic effect was found when IL-7 and other cytokines were added to cells from the 3 patients with CD7+4-8- acute leukemia who were tested.
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PMID:Effects of interleukins 1-7 on the proliferation of T-lineage acute lymphoblastic leukemia cells. 176 57

The receptor for human macrophage colony stimulating factor (CSF-1R) was introduced into hematopoietic cell lines of myeloid and T-lymphoid origin, both of which normally do not express the CSF-1R. Infection of an interleukin-3 (IL-3)-dependent mouse myeloid cell line (FDC-P1) with a high titer retroviral vector expressing the human c-fms c-DNA, enabled CSF-1-dependent proliferation in short-term liquid culture assays as well as in clonal culture systems. CSF-1-dependent cell lines could be established after sorting for CSF-1R positive cells. In contrast to FDC-P1 cells, expression of the CSF-1R in CTLL cells, an IL-2-dependent mouse cytotoxic T-cell line, and in T-cell growth factor III/P40-dependent helper T-cells, ST2/K9.4a2, did not lead to CSF-1-dependent proliferation. These observations lead to the conclusion that ectopically expressed CSF-1R may function on certain myeloid cells where it is normally not expressed, suggesting the presence of signal transduction pathways which can be utilized by that foreign receptor. In contrast, it appears that T-lymphoid cells lack such a signalling mechanism, indicating that quite different modes of transducing mitogenic signals from the cell membrane to the nucleus must have developed during myeloid and T-lymphoid differentiation.
Leukemia 1991 Jan
PMID:Expression of human CSF-1 receptor induces CSF-1-dependent proliferation in murine myeloid but not in T-lymphoid cells. 182 80

Four human leukemic T-cell lines with a T-cell receptor (TCR) gamma/delta heterodimer (MOLT-13, MOLT-14, and PEER) or beta/delta-heterodimer (DND-41), as determined by monoclonal antibody (mAb), TCR delta-1, were identified by phenotypic and genotypic analysis. Two similar human leukemic T-cell lines with a TCR alpha/beta heterodimer (CCRF-CEM and MOLT-16) were used in this study. Natural killer (NK)-like activity was investigated in the TCR gamma/delta+ cell lines and TCR alpha/beta+ cell lines induced by exogenous recombinant human IL-2 (rIL-2), or phorbol 12-myristate 13-acetate (PMA). Three (MOLT-13, MOLT-14, and DND-41 cells) of the four TCR delta-1 positive cell lines, after 48 h treatment with exogenous rIL-2 or PMA (except DND-41), showed NK-like activity to K562, but not to Daudi cells. Furthermore, when MOLT-13, MOLT-14, and DND-41 cells were co-cultured with rIL-2 or PMA, 5-20% of these cells expressed the beta-subunit of IL-2R. Treatment with rIL-2 or PMA induced the expression of the beta-subunit of IL-2R, which in turn induced IL-2R. Subsequently these cells could transmit the signal for the induction of NK-like cytotoxicity. These findings indicate that changes in the beta-subunit of IL-2R expression may be responsible for the target cell specificity of activated effector cells.
Leukemia 1991 Sep
PMID:Induced natural killer-like cytotoxic function in the TCR delta-1 positive human leukemic T-cell lines. 183 94

A human leukemia cell-derived suppressor factor (LDSF) capable of suppressing in vitro proliferation and activation of normal human lymphocytes was purified from human leukemic HL-60 cells. LDSF is constitutively produced by the cells and was purified from serum free culture supernatant by a combination of ion-exchange chromatography, gel filtration and electrophoresis. Purified LDSF was determined to be a single chain protein with an apparent molecular mass of 66,000 daltons. LDSF was not cytolytic to lymphocytes, was heat stable at 70 degrees C, and did not have any effect on IL-2 or transferrin receptor expression.
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PMID:Purification and characterization of a human leukemia cell-derived immunosuppressive factor. 185 82

Adult T-cell leukemia (ATL) cells have been shown to express the receptor for IL-2 by studies using anti-CD25 monoclonal antibody, but these cells usually show no or only a weak proliferative response to IL-2. In the present study, we established thirteen IL-2-dependent T-cell lines from four ATL patients. Examination of the clonalities of these cell lines by the rearrangement profiles of the TCR beta-chain gene and the integration sites of the HTLV-I proviral genome, revealed that two cell lines (KK-1 and KK-5) were of real ATL cell origin. The others were of normal T-cell origin and had been established by infection with HTLV-I. The KK-1 and KK-5 cell lines were derived from a single ATL patient (KK). Interestingly, these cells showed different phenotypic features from the majority of original leukemia cells (CD3 +/- CD4+ CD8-). The KK-1 cell line acquired CD8 antigen expression and became double-positive (CD3 +/- CD4+ CD8+), while the KK-5 cell line prominently expressed CD3 antigen (CD3+ CD4+ CD8-). These results indicate that the phenotypic feature of ATL cells are not fixed, but can change in vitro as has occasionally been observed in vivo.
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PMID:IL-2-dependent ATL cell lines with phenotypes differing from the original leukemia cells. 186 43


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