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)

We have produced a monoclonal antibody (MoAb), AML-1-99, that defines a novel 124-kd protein antigen expressed on a subpopulation of monocytes and on the majority of hematopoietic progenitor cells of the granulocyte-monocyte (CFU-GM), erythroid, and mixed-lineage classes. AML-1-99 is lytic to bone marrow (BM)- and peripheral blood-derived progenitor cells in the presence of rabbit complement (C'). AML-1-99 is not toxic to progenitor cells in the absence of C', nor does it modify their growth when included in colony-forming cultures. Several leukemia cell lines, including HL-60, U937, KG-1a, and Daudi cells, express the antigen on the majority of cells. Freshly isolated leukemia cells from patients with acute myelogenous leukemia (AML) react variably with AML-1-99. Leukemia colony-forming cells from several AML patients express the antigen and could be eliminated by treatment with AML-1-99 and C'. Cell sorting and immune rosette techniques were successfully applied to normal BM and chronic myelocytic leukemia cell populations using AML-1-99 with the result that significant enrichment of CFU-GM could be accomplished. The pattern of reactivity of this MoAb and its apparent molecular weight suggests that AML-1-99 recognizes a newly defined myeloid-associated cell surface antigen.
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PMID:Distribution of the 124-kd antigen defined by monoclonal antibody AML-1-99 on normal and leukemic myeloid cells. 342 92

A B16 melanoma clone and four derived subclones exhibiting markedly different tumorigenic and metastatic potentials in young C57BL/6 mice were investigated comparatively to determine relative immunogenicities and capacities to induce humoral and cell-mediated immune responses following subcutaneous injection. All five populations stimulated some production of circulating antibody to a cell surface antigen complex (B16-gp70/80/85) specified by endogenous murine leukemia virus, as well as spleen-cell-mediated cytolytic and cytostatic activity apparently directed to the same antigens, but to varying extents. Immunogenicity and relative capacity to induce immunity were inversely related to tumorigenicity and tumor growth rate but were not obviously correlated with metastatic behavior. There were indications that tumor behavior might be influenced by developing or naturally acquired host immunity. The most rapidly growing clone, G3.26, which was poorly immunogenic and nonmetastatic in young mice, grew more slowly and was markedly metastatic in normal-aged mice in which some natural humoral and cellular responses cross-reactive with B16-gp70/80/85 antigens were detected. Furthermore, the highly immunogenic and normally nonmetastatic clone, G3.15, was appreciably metastatic in mice immunosuppressed by T lymphocyte depletion. In other cases, however, tumor behavior in immunosuppressed and immunopotentiated mice did not consistently indicate a critical role for host immunity in determining metastatic or nonmetastatic activity.
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PMID:Development of host immunity to phenotypically diverse B16 melanoma clones. Implications for tumor growth and metastasis. 343 37

In this study, a monoclonal antibody (mAb) termed SN6 was generated by immunizing a mouse with a non-T-cell leukemia antigen preparation isolated from cell membranes of leukemia cells derived from a patient (FJ) with non-T/non-B-cell-type acute lymphoblastic leukemia (ALL). SN6 was tested against a variety of cultured and uncultured human cell specimens by using a sensitive cellular radioimmunoassay. Among the 26 cultured malignant and nonmalignant cell lines tested, SN6 reacted with all of the 6 leukemic non-T/non-B (including pre-B)-cell lines tested--i.e., KM-3, NALM-16, REH, NALL-1, NALM-1, and NALM-6. Of these cell lines, 5 were derived from individual patients with ALL; the remaining 1 was from a patient with chronic myelocytic leukemia in blast crisis. In addition, SN6 reacted with 3 of 3 leukemic myelo-monocytic cell lines tested--i.e., ML-2, HL-60, and U937. SN6 did not react with any other cell lines. A consistent result was obtained with 42 fresh (uncultured) cell specimens derived from individual patients with several different types of leukemias. SN6 reacted with 11 of 16 non-T/non-B (including pre-B)-cell ALL specimens. In addition, it reacted with various myelo-monocytic leukemia cell specimens to various degrees. SN6 did not show a significant reaction with normal peripheral blood cells tested, which included B cells, T cells, granulocytes, monocytes, and erythrocytes. However, it reacted with a small population (approximately 1% as determined by immunofluorescence staining) of normal bone marrow cells. The approximate molecular mass of the glycoprotein antigen defined by SN6 was determined to be 160,000 by radioimmunoprecipitation followed by sodium dodecyl sulfate/polyacrylamide gel electrophoresis. Only one component of 80,000 daltons was formed upon reduction of the 160,000 molecular mass antigen. Therefore, this antigen is apparently a homodimer of a 80,000-dalton subunit. This conclusion was further corroborated by two-dimensional gel analysis, which showed a single well-defined spot for the reduced antigen. We designate this distinct human leukemia-associated cell surface antigen "GP160."
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PMID:Distinct human leukemia-associated cell surface glycoprotein GP160 defined by monoclonal antibody SN6. 346 4

Monoclonal antibodies (MoAb) to a leukemia-associated p24 cell surface antigen are currently being used to purge bone marrow of malignant cells before autologous transplantation for acute lymphoblastic leukemia (ALL). Their use as potential diagnostic reagents for hematologic disorders is also under investigation. It has been assumed throughout these investigations that the p24-specific MoAb produced by different laboratories all identify the same antigen. Our present studies indicate that at least two populations of p24 antigens, having different chemical properties and cellular distributions, exist on malignant B cells. For example, eight MoAb raised to ALL cells (ALL-MoAb) identify a p24 antigen on these cells but do not react with the Burkitt's lymphoma cell line Ramos. In contrast, six MoAb raised to Ramos (Ramos-MoAb) identify a p24 antigen on both Ramos and ALL cells. Quantitative binding of both sets of MoAb to ALL cells is comparable. The ALL-MoAb react with platelets, granulocytes, and activated but not resting T lymphocytes, whereas the Ramos-MoAb react with both resting and activated T lymphocytes but not with platelets or granulocytes. The ALL-MoAb react with 11 of 34 human hematopoietic cell lines tested; the Ramos-MoAb react with all 34. Both sets of MoAb react with most of the nonhematopoietic human cell lines tested. Reciprocal exhaustive radioimmune precipitation experiments performed with an ALL cell line indicate that the antigenic determinants recognized by these two sets of MoAb are present on different molecules. Similarly, proteolytic digests of iodinated antigens identified by these two sets of MoAb on ALL cells confirm the unique chemical identities of these molecules and suggest that they reflect the products of different genetic loci. The presence of the antigen identified by the Ramos-MoAb on every cell population tested except granulocytes suggests that it may serve an important cellular function. The existence of two populations of p24 antigens on at least some hematopoietic cells indicates the need for caution when comparing the results of studies of these antigens by groups employing different MoAb.
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PMID:Malignant human B cells express two populations of p24 surface antigens. 348 54

The specificity of CTL generated against tumors induced by murine leukemia viruses (MuLV) has been reported to parallel the expression of two serologically defined tumor cell surface antigens--the cross-reactive FMR antigen expressed on the surface of tumors induced by Friend, Moloney, and Rauscher MuLV, and the Gross cell surface antigen (GCSA) expressed on tumors induced by AKV/Gross MuLV. We examined the specificity of CTL generated against MuLV-induced tumors and identified two distinct patterns of reactivity. The first follows the traditional pattern of FMR vs GCSA reactivity as assessed on a panel of established MuLV-induced lymphomas. However, CTL exhibiting this pattern of reactivity are incapable of lysing MuLV-infected fibroblasts. CTL exhibiting the second pattern of reactivity are capable of lysing MuLV-induced lymphomas as well as MuLV-infected fibroblasts. In addition, these CTL exhibit extensive cross-reactivity between lymphomas and fibroblasts infected by both groups of MuLV. Our results suggest that CTL exhibiting the traditional FMR vs GCSA pattern of reactivity are directed against a tumor-associated antigen and not against virus-encoded antigens, and that CTL directed against MuLV-encoded antigens demonstrate extensive cross-reactivity, including the ability to lyse AKV-infected cells.
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PMID:The immune response to Moloney murine leukemia virus-induced tumors: induction of cytolytic T lymphocytes specific for both viral and tumor-associated antigens. 349 Nov 52

The tumor-associated surface antigen on L1210 leukemia cells was studied by immunofluorescence staining and immunoprecipitation. Anti-L1210 serum was prepared in BALB/c X DBA/2 F1 mice by priming with a hybrid of L1210 and human Lesch-Nyhan fibroblast cells and hyperimmunizing with L1210 leukemia cells. This hyperimmune serum was able to demonstrate specific surface fluorescence on L1210 cells, while the antiserum did not react with various mouse tumor cell lines, normal lymphoid tissues, or mitogen-activated lymphoid cells. The anti-L1210 serum immunoprecipitated a single polypeptide with a molecular weight of 90,000 from 125I-labeled L1210 cells. The expression of this antigen was enhanced by tumor-promoting agent and heat shock treatment. The biological significance of the L1210-specific cell surface antigen is discussed.
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PMID:Identification and characterization of a unique tumor-associated surface antigen on L1210 leukemia cells recognized by semisyngeneic antisera. 354 98

We have studied the potential use of immunotoxins (ITs) for therapeutic treatment of human tumors in an experimental model of human neoplasia. We tested intact ricin IT for its antitumor activity against established tumors. CEM, a human T-cell leukemia line expressing an Mr 67,000 cell surface antigen, and Daudi, a human B-cell lymphoma line which does not express the antigen, were found to be consistently tumorigenic in nude mice. ITs were synthesized using T101, a high-affinity monoclonal antibody reacting with the Mr 67,000 protein determinant and intact ricin. We have shown for the first time that established CEM solid tumors in nude mice will regress following intratumoral injection of T101-ricin IT, while Daudi tumors will not. Selective activity of T101-ricin is dependent on systemic i.v. administration of lactose and local intratumoral injection of the T101-ricin IT with lactose. Intact ricin ITs require the presence of lactose to block native ricin binding and render them antigen specific when linked to monoclonal antibody. Killing of target was cell specific since (a) nonspecific (irrelevant) ITs did not cause the regression of CEM tumors, and (b) injection of large amounts of free T101 antibody prior to T101-ricin IT blocked antitumor activity. Selectivity was not absolute, since regression occurred in one of six animals given irrelevant IT, and blocking was observed in two of four mice. Intratumoral IT treatment with 1 or 2 micrograms of T101-ricin IT plus lactose was not harmful to mice in contrast to intratumoral ricin treatment, which killed all treated tumor-bearing mice at a dose of 0.3 micrograms. Without i.v. injection of lactose, intratumoral injection of T101-ricin IT was also effective in eliminating established tumors. However, this treatment did not result in the selective elimination of tumor, since Daudi tumors also regressed following T101-ricin IT treatment. IT, made with ricin A chain only (T101-A chain IT), was also tested against established CEM tumors. We found that high dosages of T101-A chain IT did not destroy CEM tumors when injected intratumorally, even in the presence of activating agents such as NH4Cl or the carboxylic ionophore X-537 A. In contrast, in vitro experiments demonstrated that T101-A chain IT plus activating agents had potent and selective cytotoxic effect against CEM cells. We conclude that ITs are specifically toxic to established tumors. Although selectivity is not absolute, ITs exhibit potential as a new class of antitumor reagents.
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PMID:Cytotoxic effect of anti-Mr 67,000 protein immunotoxins on human tumors in a nude mouse model. 397 76

We have shown previously that the serologic response of BALB/c mice to immunization with BALB/c sarcoma Meth A cells can be more effectively augmented by pretreatment with cyclophosphamide (Cy) than by the use of adjuvants. The serologic response was directed against a highly restricted cell surface antigen, closely related to or identical with the unique transplantation antigen characteristic for this tumor. In this paper, we report the results of our attempts to obtain additional augmentation by using Cy and adjuvants together. For these studies, the optimal Cy dose, interval between Cy and vaccine administration, and vaccine cell number were determined. Mice were injected with Cy 25 mg/kg i.p., and 3 days later, with viable irradiated (10,000 rad) Meth A cells subcutaneously, under conditions in which only few mice produced antibody. Sera were tested for antibody with reactivity against Meth A by complement dependent cytotoxicity (CDCX), which predominantly detects IgM, and by the protein A (PA) and anti-IgG assays, which detect IgG. Of the various adjuvants tested, only monophosphoryl lipid A (MPLA) and CP20,961 resulted in significantly increased titers of reactivity in both the CDCX and PA assays over that obtained when using Cy alone. Although the mean titers observed with CDCX ranged between 1/160 and 1/320, no titer above 1/40 was observed with the PA assay. The specificity of the CDCX reactivity detected by the assay for the Meth A antigen was ascertained by absorption analysis of selected sera by using a panel of BALB/c spleen and tumor cell lines grown in vitro or in vivo. PA titers were too low to permit absorption analysis, and the titers obtained in the anti-IgG assay were lower still. Attempts to augment the anti-Meth A IgG response or to convert the IgM response to IgG were unsuccessful. The combined approach described here (i.e., vaccination with irradiated syngeneic tumor cells plus MPLA in Cy-pretreated mice) was also shown to be effective in augmenting the serologic response against two additional murine leukemia virus-negative sarcomas that are known to be less immunogenic, CMS4 and CMS5. It appears, therefore, that this combined approach may be applicable to stimulating serologic responses against a variety of tumor cell surface antigens.
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PMID:The serologic response to Meth A sarcoma vaccines after cyclophosphamide treatment is additionally increased by various adjuvants. 400 30

A mouse monoclonal antibody, WM-15, has been developed which reacts with a human myeloid lineage-restricted cell surface antigen. WM-15, an IgG1 antibody, reacts with a mean of 3.8% of normal bone marrow mononuclear cells, identifying predominantly promyelocytes and myeloblasts, and in fluorescence-activated cell sorting experiments produces enrichment of bone marrow granulocyte-macrophage progenitor cells. Normal mature monocytes and granulocytes are weakly labelled by WM-15, but other haemopoietic cells including erythroblasts and all lymphoid cells are unreactive. The myeloid specificity of this antibody is highlighted by its reactivity with myeloid leukaemia cell lines and 65% of cases of acute myeloid leukaemia, while lymphoid cell lines and leukaemias are WM-15 negative. WM-15 appears to be a useful reagent for further investigation of normal and abnormal myelopoiesis.
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PMID:Myeloid progenitor surface antigen identified by monoclonal antibody. 405 21

The 8303 hamster tumor cells transformed by Moloney strain of murine sarcoma virus (M-MSV), but which do not produce virus, do contain murine virus-induced proteins. The virus-induced proteins within the cell were identified either as free proteins or in association with membranous material, including the plasma membrane. In addition, some were excreted by the 8303 hamster tumor cells into the growth medium. Most virus-induced proteins were larger than 68,000 daltons, and they did not dissociate into components of smaller size in the presence of detergent and a reducing agent. A small amount of virus-induced protein with a molecular weight of less than 20,000 was also found in the hamster tumor cells. No virus-specific proteins with the identical antigenic specificity or size of the major internal group specific antigen (molecular weight about 30,000) of the murine leukemia viruses were present in these cells. There is a common cell surface antigen present in three other tumor cell lines, both virus-producing and non-virus-producing, identical in reactivity to that of the murine virus-induced antigen of the 8303 hamster tumor cell. This antigen is not present on the cell surface of normal mouse embryo cells.
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PMID:Murine virus-induced proteins synthesized by hamster tumor cells transformed by, but not producing, murine sarcoma virus. 435 2


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