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

The distribution of the normal differentiation antigen Thy 1 and the mammary tumor virus (MTV)-induced antigens or antigen complexes MLm and MLr were studied in mouse mammary gland cells, mammary tumor cells, and other cell types, by use of ascites leukemia cells of the GR mouse strain as target cells in the cytotoxicity test. The Thy 1.2 antigen was detected by an AKR antiserum to C3Hf thymocytes. MLm was shown by a homologous C57BL antiserum to GRSL2 leukemia (absorbed in vivo in GR mice); MLr was detected by a rabbit heterologous antiserum (absorbed in vivo in C57BL or GR mice and in vitro with BALB/c milk) prepared against Tween 80- and ether-treated purified B particles. Sera from Sprague-Dawley rats bearing murine leukemia virus (MuLV)-producing syngeneic tumors were not cytotoxic or only slightly cytotoxic for GR leukemias transplanted in vivo, which indicated that MuLV-induced antigens were absent or present in very low quantity in such leukemias. The MLr and MLn antigens or antigen complexes were possibly identical to the mammary leukemia (ML) antigen, since they could be detected not only on GR but also on DBA/2 leukemia cells and since their distribution was exactly the same as that of MTV. Both the MLr and MLm antigens were present in purified B particles, and antigenic activity were present in purified B particles, and antigenic activity was enhanced by destruction of the purified virus particles. The antigens were about eightfold enriched in a preparation of B-particle envelopes, as shown by quantitative cytotoxicity absorption (CYTA) tests. Purified nucleoid fractions of B particles were only lightly positive for the antigen, probably due to envelope contamination. One dominant gene was responsible for the expression of MLr, as shown by CYTA tests with mammary glands of individual animals of segregating crosses between the GR strain with high mammary cancer incidence and strains with low incidence. This gene was closely linked with or was possibly identical to 1) the gene for cytoplasmic MTV gs antigen expression as seen by fixed cell immunofluorescence, and 2) the gene causing mammary tumors in the GR mouse strain.
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PMID:Immunologic, virologic, and genetic aspects of mammary tumor virus-induced cell-surface antigens: presence of these antigens and the Thy 1.2 antigen on murine mammary gland and tumor cells. 16 86

Based on the presence or absence of erythrocyte receptors(E) a T cell marker, acute lymphocytic leukemia (ALL), can be divided into E+ALL and E-ALL. We studied cell surface antigens on blasts from 12 children with untreated ALL: eight with E-ALL and four with E+ALL. Heterologous antisera were raised against thymus cells, E+ and E-ALL blasts, appropriately absorbed and tested by immunofluorescence and a radiolabeled antibody assay with normal and leukemic lymphoid cells. By both methods, anti-thymus and anti-E+ALL sera reacted with human thymocytes. Specific binding of anti-E+ALL serum to T antigens was indicated by the fact that a single absorption with thymocytes abolished its binding to allogenic thymocytes, and the reactivity of anti-E+ALL serum with thymus, blood and bone marrow lymphocytes was similar to that of anti-thymus serum. After exhaustive absorption with blood leukocytes, anti-E+ALL and E-ALL sera were negative against normal lymphocytes and bone marrow cells from children with ALL in remission. Anti-thymus and anti-E+ALL sera reacted with blasts from patients with E+ALL, but not with E-ALL. In contrast, anti-E+ALL serum reacted with 40 to 96% of blasts from all children with E-ALL, whereas of the four patients with E+ALL, two were negative and two had the lowest percentage of immunofluorescent cells (10 to 22%). These results were confirmed with the radiolabeled antibody assay. Patients with active E-ALL had cells bearing E-ALL antigen(s) in the peripheral blood and bone marrow, but the number of immunofluorescent cells was lower in blood. Cells reactive with anti-E-ALL serum did not react with thymus cells, blood lymphocytes, remission bone marrow cells, Raji cells, PWM and PHA-induced blasts and CLL cells bearing mIg (uk). These data suggest that the antigen detected on E-ALL blasts by anti-E-ALL serum is neither a HLA-related nor a cell differentiation antigen. Thus, by using antiserum to E+ALL blasts, we have confirmed the presence of a T cell-specific antigen(s) on E+ALL cells. This antiserum did not recognize other leukemia-associated antigens common to E+ and E-ALL. We have also demonstrated an antigen(s) which is regularly expressed on E-ALL blasts and is either not detectable or is present in a lower proportion of E+ALL blasts.
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PMID:Acute lymphoblastic leukemia (ALL) antigens detected with antisera to E rosette-froming and non-E rosette-forming ALL blasts. 31 69

The distinction of clonogenic leukemic cells (CFU-L) and normal myeloid progenitors (GM-CFU) is a problem because both types of cells respond to the same growth factors and their clones resemble each other morphologically in culture. We investigated by means of an indirect enzyme-immunoassay the expression of "early" and "late" differentiation markers on bone marrow cell suspensions, as well as on agar clones in 18 cases of newly diagnosed acute myeloid leukemia (AML) as compared with 13 normal controls. Uncultured AML cells carried only low amounts of "late" myeloid differentiation antigen (CD15) but expressed nearly normal levels when cultured in agar with colony-stimulating factor (CSF). In contrast to normal bone marrow, AML cells were strongly reactive with "early" differentiation markers (CD10, CD20, CD34) and remained so during culture. Normal and leukemic agar clones could be specifically distinguished by CD20- and CD34 antibodies. By means of a double marker technique, it could be shown that "late" myeloid differentiation markers (CD15) and "early" markers (CD10, CD20, CD34) were coexpressed on the same cells only in AML but not in normal bone marrow. Leukemic clones were identified by phenotyping of agar clones in 17 of 19 cases investigated during complete clinical remission (CR) of the disease. A formal proof of the leukemic origin of CD20/CD34 positive clones grown in CR was made possible in four cases either by Southern blot analysis or by a cytogenetic marker. These results demonstrate that AML cells can partially differentiate in vitro in the presence of CSF. A distinction of AML from normal clones, however, is possible by their reactivity with "early" differentiation markers, because this is maintained under the differentiating influence of CSF. The technique described here identifies residual leukemic clones in the majority of AML in CR, which persist at a constant rate and increase 6 months before cytological relapse.
Leukemia 1990 Jul
PMID:Detection of minimal residual disease in acute myeloid leukemia. 169 5

The anticancer drug mitomycin C (MMC) was conjugated with an affinity-purified murine monoclonal antibody (HI30) to a human T lymphocyte surface differentiation antigen with dextran T-40 as the intermediate carrier. The conjugate (HI30:MMC molar ratio, 1:7) retained full antibody binding activity as determined by an indirect immunofluorescence assay. E. Coli HB101 growth inhibition test showed that the antimicrobial activity [MMC equivalent (microgram/ml)] of the conjugate was about 29.2% as potent as free MMC. In a cytotoxicity test, the conjugate was about 3-10 times more cytotoxic against the antibody-reactive human T lymphocyte leukemia CEM cells than was free MMC or the mixture of HI30 and MMC [IC50 of the MMC equivalent (microgram/ml) was 0.4147, 2.212, 2.171, respectively] and was less cytotoxic against the antibody-nonreactive L1210 cells (IC50 were 1.311, 0.8683, 0.7308, respectively). The selective cytotoxicity was also confirmed by competitive inhibition with free antibody, showing a dependence on antibody binding of the target cell surface antigen. There was no detectable free MMC released from HI30-Dex-MMC conjugate stored at 4 degrees C for over one month as measured by chromatography on a Sephadex G-25 column.
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PMID:[Preparation of a monoclonal antibody (HI30)-mitomycin C conjugate utilizing dextran T-40 and its specific cytotoxicity against human leukemia cell line CEM]. 170 60

Differentiation of a human eosinophilic leukemia cell line, EoL-1, induced by the culture supernatant of a human ATL cell line, HIL-3 (HIL-3 sup) was compared with differentiation induced by defined cytokines. HIL-3 sup induced EoL-1 cells to express eosinophilic granules and segmented nuclei after 6 to 9 days of incubation. HIL-3 sup also induced the expression of Fc epsilon receptor II (Fc epsilon RII/CD23) and an eosinophil differentiation antigen EO-1 mainly on eosinophilic granule (+) cells. Furthermore, HIL-3 sup induced EoL-1 cells to respond to an eosinophil chemotactic factor, platelet activating factor. HIL-3 cells express messenger RNA (mRNA) of interleukin-5 (IL-5), macrophage colony-stimulating factor (M-CSF), and IL-3 but not granulocyte CSF (G-CSF). Granulocyte-macrophage CSF (GM-CSF) and tumor necrosis factor-alpha (TNF-alpha) were detected in the HIL-3 sup. Recombinant IL-2 (rIL-2), rIL-3, rIL-4, rIL-5, rM-CSF, and rGM-CSF did not induce eosinophilic granules. rG-CSF induced a few eosinophilic granule (+) cells, and TNF-alpha, which did not induce eosinophilic granules by itself, enhanced the ability of G-CSF to induce them. However, G-CSF and TNF-alpha did not induce the expression of Fc epsilon RII and EO-1 antigen. Moreover, anti-G-CSF, anti-TNF-alpha, anti-GM-CSF, anti-IL-3, and anti-IL-5 antibodies did not suppress the effect of HIL-3 sup on the differentiation of EoL-1 cells. All the data suggest that HIL-3 sup contains an unidentified factor that induces differentiation of EoL-1 cells, and that EoL-1 cells and HIL-3 sup provide an important model for the examination of differentiation mechanisms and functions of eosinophils.
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PMID:Differentiation of a human eosinophilic leukemia cell line (EoL-1) by a human T-cell leukemia cell line (HIL-3)-derived factor. 170 98

The rejection of allografts is mediated by cytolytic T cells and antibody-secreting B cells. Selective ablation of these activated cells from peripheral blood lymphocytes may offer a a method of controlling allograft rejection. An immunotoxin was prepared from the monoclonal antibody (mAb) NDA 4, which recognizes a differentiation antigen (NDA 4) common to activated B and T cells. MAb NDA 4 was conjugated to the ribosome-inhibiting protein gelonin via a cleavable disulfide bond provided by a crosslinking reagent. The purified immunotoxin was evaluated for in vitro cytotoxicity on NDA 4 positive T and B cell lines. Conjugation of mAb NDA 4 to gelonin increased the in vitro cytotoxicity by a concentration factor of 1000, compared to gelonin alone. The specificity and saturability of mAb NDA 4 binding, as well as the number of antigenic sites per cell on resting versus activated T lymphocytes, were also evaluated. Resting T cells expressed 400-800 sites per cell. PHA-activated T cells and the MLA T cell leukemia expressed 10,000 to 80,000 sites per cell. Peripheral blood mononuclear cells obtained from allografted baboons in quiescence or undergoing rejection were compared for NDA 4 expression by flow cytometry. Lymphocytes obtained from baboons rejecting a heart allograft expressed NDA 4, whereas transplant recipients in quiescence showed no detectable NDA 4. These results suggest that mAb NDA 4-derived immunotoxins may be valuable for the selective depletion of activated lymphocytes while sparing the resting population.
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PMID:In vitro studies of the effect of MAb NDA 4 linked to toxin on the proliferation of a human EBV-transformed lymphoblastoid B cell line and of gibbon MLA leukemia cell line. 184 63

The endocytosis of the T cell differentiation antigen CD4 has been investigated in CD4-transfected HeLa cells, the promyelocytic HL-60 cell line, and in a number of leukemia- or lymphoma-derived T cell lines. CD4 internalization was followed using radioiodinated antibodies in an acid-elution endocytosis assay, or by covalently modifying cell surface proteins with biotin and analyzing CD4 distributions by immunoprecipitation; both approaches gave equivalent results. The assays demonstrated that in transfected HeLa cells and in HL-60 cells CD4 was constitutively internalized and recycled in the absence of ligand. Immunogold labeling and electron microscopy demonstrated that CD4 enters cells through coated pits. In contrast to the nonlymphocytic cells, T cell lines showed very little endocytosis of CD4. Measurements of fluid phase endocytosis and morphometric analysis of the endosome compartment indicated that the endocytic capacities of HeLa and lymphoid cells are equivalent and suggested that the low level of CD4 uptake in lymphocytic cells is due to exclusion of CD4 from coated pits. This conclusion was supported by experiments using truncated CD4 molecules, lacking the bulk of the cytoplasmic domain, which were internalized equally efficiently in both transfected lymphocytes and HeLa cells. Together, these results indicate that the cytoplasmic domain of CD4 mediates the different interactions with the endocytic apparatus in lymphoid and nonlymphoid cells. We suggest that the CD4-associated lymphocyte-specific protein tyrosine kinase p56lck may be involved in preventing CD4 endocytosis in T cells.
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PMID:Differential endocytosis of CD4 in lymphocytic and nonlymphocytic cells. 190 77

Trans-activating activities of certain cellular promoter/enhancer genes may reflect the underlying mechanism for cellular differentiation. We have used two promonocytic leukemia cell lines, U937 and HL-CZ, which differ in their differentiation antigen expression. While both cell lines express CD15 antigen, only the former expresses both CD4 and CD10 antigens. These phenotypes suggest that these two cell lines appear to be arrested at different stages of differentiation. Some regions of the long terminal repeat (LTR) of human immunodeficiency virus-1 (HIV-1) contain nucleotide sequences which bind cellular trans-activating factors such as NF-kappa B and Sp1. These sequences are also present in cellular regulatory gene sequences. The cell lines have been transfected by electroporation with a nested series of deletion mutants containing different lengths of the promoter/enhancer region for HIV-LTR. The promoter/enhancer region has been linked to a 'reporter' chloramphenicol acetyl transferase (CAT) gene. We have found that promoter/enhancer trans-activation is markedly enhanced by treating transfected cells with 12-O-tetradecanoylphorbol-13-acetate (TPA), while similar treatment with tumor necrosis factor-alpha (TNF alpha) slightly enhanced activation. U937 cells always showed much greater transactivating activities than did HL-CZ cells. Deletion of a negative regulatory element (NRE) from the LTR resulted in an enhanced transactivation, while deletions affecting NF-kappa B and/or Sp1 binding sites markedly reduced transactivation. Deletion of both NRE and NRF, a second negative regulatory factor binding site, from the LTR restored the transactivation. However, in the presence of TPA, deletion of NRE sequence without concomitant deletion of the downstream NRF binding sequence was sufficient for recovering transactivation. Since these two cell lines have shown subtle differences in these responses, it may be speculated that monocytes at different stages of differentiation may respond in different ways, qualitatively and/or quantitatively, to signal transduction factors involved in the transactivation of cellular genes.
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PMID:Regulation of cellular trans-activating activities in two different promonocytic leukemia cell lines. 191 29

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

This report describes the characterization and expression of a human myeloid differentiation antigen defined by use of an IgG1 monoclonal antibody (AHN-7). This antibody binds to many granulocytic precursors in normal marrow, to most but not all granulocyte-macrophage progenitors (CFU-GM), and to approximately half of nonlymphoid leukemia specimens. The protein antigens recognized by AHN-7 were purified from 35S-labelled HL-60 cells by antibody affinity column chromatography. The molecule reacting with AHN-7 was markedly heterogeneous, appearing as several forms ranging in pl from 4.5 to 6.4 with apparent molecular weights from 43,000 to 68,000. The molecules were not disulfide-linked. Proteins bearing the antigen were minor components of the plasma membrane. The antigen was expressed by normal human peripheral blood neutrophils, monocytes, eosinophils, and basophils, and weakly on a small percentage of lymphocytes; it was not detected in red blood cells, platelets, or the majority of lymphocytes. The antibody also bound to a variety of human myeloid leukemia cell lines but not to any lymphoid leukemia cell line tested. AHN-7 had no effect on several in vitro neutrophil functions tested.
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PMID:Identification and purification of the human myeloid differentiation antigen recognized by monoclonal antibody AHN-7. 243 75


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