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E D Ball

Publications and source records attributed to E D Ball.

119 records · Page 7Linked to original sources
PubMed1983

The expression and modulation of human myeloid-specific antigens during differentiation of the HL-60 cell line.

Antigenic changes detected by myeloid-specific monoclonal antibodies on HL-60 cells induced to differentiate by various chemical mediators were investigated using flow cytometry. Antigen levels detected by monocyte-granulocyte-specific monoclonal antibodies AML-2-23, 61D3, and 63D3 increased dramatically after differentiation of HL-60 cells along the granulocytic pathway by the addition of dimethyl formamide (DMF), dimethylsulfoxide (DMSO), or cis-retinoic acid. The expression of these same antigens also increased in conjunction with monocytoid differentiation when HL-60 cells were treated with supernatants from leukocytes stimulated with phytohemagglutinin (PHA-LCM) or with mixed lymphocyte conditioned medium (MLC). In contrast, treatment of HL-60 cells with phorbol 12-myristate 13-acetate (PMA), which also induced differentiation along the monocyte pathway, had no effect on the expression of these monocyte-associated antigens. The expression of antigens on HL-60 cells recognized by the granulocyte-specified monoclonal antibodies PMN 6 and PMN 29 decreased after treatment of HL-60 cells with PMA, but remained constant after treatment with DMF, DMSO, cis-retinoic acid, PHA-LCM, or MLC. These results suggest that normal myeloid differentiation may be dependent on various signals and that morphological and cell surface marker maturity may, under some conditions, be separable. The utility of the HL-60 cell line as a model of myeloid differentiation and for evaluation of inductive signals is discussed.

Animals↗
PubMed1983

The use of myeloid-specific monoclonal antibodies in the diagnosis of leukemia.

Leukemia cells express a variety of cell surface antigens that have been useful in the delineation of subclasses of both lymphocytic and myeloid leukemia. In this report we describe the phenotype of cells from 50 patients with leukemia based on the results of testing for binding to four monoclonal antibodies reactive with myeloid cell-associated antigens and, in some cases, three monoclonal antibodies reactive with lymphocyte-associated antigens. We related the patterns of reactivity of these leukemia cells with the diagnosis based on morphology and histochemistry. Three of the myeloid cell-associated antigens (PMN 6, PMN 29, and AML-2-23) were expressed only on cells from patients with AML. The fourth, PM-81, was expressed on cells from 29/31 patients with AML and on 3/5 with ALL. The reactivity of the ALL cells with the J5 and B1 antibodies confirmed the diagnosis of ALL. A proposed schema for the use of these monoclonal antibodies in both the diagnosis and subclassification of leukemia is described. Finally, the significance of the heterogeneity in antigen density on leukemia cells is considered.

Animals↗
PubMed1983

A unique antigen expressed on myeloid cells and acute leukemia blast cells defined by a monoclonal antibody.

A murine hybridoma-derived monoclonal antibody, PM-81, was obtained from a fusion of cells of the NS-1 myeloma cell line with cells from a mouse immunized with the HL-60 promyelocytic leukemia cell line. This cytotoxic IgM monoclonal antibody was specific for myeloid cells. Employing indirect immunofluorescence and flow cytometry, we determined that this antibody reacts strongly with normal human granulocytes, eosinophils, and monocytes but not lymphocytes (including phytohemagglutinin-activated lymphocytes), null cells, red blood cells, or platelets. Moreover, the PM-81 antibody reacts with leukemia cells from 19 of 22 patients with acute myelocytic leukemia of all FAB subclasses, three of three patients with common acute lymphocytic leukemia, four of four patients with chronic myelocytic leukemia (CML) in myeloid blast crisis (terminal transferase (TdT)-negative) but did not react with cells from two patients with CML in lymphoid blast crisis (TdT-positive) or five patients with chronic lymphocytic leukemia. The myeloid cell lines HL-60, K562, KG-1, and U937 were all reactive with PM-81. The lymphoid lines CCRF-CEM and Daudi did not express PM-81 but HSB-2 was positive. The PM-81 antigen was absent on myeloid and erythroid progenitor cells as determined by their insusceptibility to complement-dependent lysis. In addition, only PM-81-unreactive cells were capable of colony formation. Furthermore, the PM-81 antibody does not appear to induce modulation of the antigen to which it binds. Thus, this monoclonal antibody appears to fulfill several criteria for clinical utility in the diagnosis and treatment of both acute myelocytic and acute lymphocytic leukemia.

Animals↗
PubMed1983

Monoclonal antibodies to myeloid differentiation antigens: in vivo studies of three patients with acute myelogenous leukemia.

Three patients with acute myelogenous leukemia (AML) in relapse were treated with intravenous infusions of one or more purified murine monoclonal antibodies (MoAbs) specific for differentiation antigens on normal and malignant myeloid cells. Three of the MoAbs used were IgM immunoglobulins that react with glycolipids, while the fourth, an IgG2b, reacts with a protein antigen. Peripheral blood leukemia cell counts decreased significantly, but transiently, during treatment. Evidence of in vivo binding of each MoAb to leukemia cells was obtained, although two of the four MoAbs could not be detected in the plasma following infusion, perhaps due to circulating blocking factors. Antigenic modulation was not encountered in these studies. However, the induction of human antibody to murine MoAb was observed in one patient who was treated over a 70-day period. Toxicities encountered were minimal and included fever (3 patients), back pain (1 patient), and arthralgias and myalgias (1 patient). This is the first reported clinical trial of (1) IgM MoAbs, (2) MoAb therapy in patients with AML, (3) combinations of MoAbs directed toward different myeloid differentiation antigens, and (4) MoAbs directed to glycolipids. The relative lack of toxicity and the positive effects of MoAb treatment in the reduction of leukemia cell counts permit the continued study of more innovative approaches to the treatment of AML with MoAbs.

Adult↗
PubMed1982

Monoclonal antibodies to novel myeloid antigens reveal human neutrophil heterogeneity.

Three cytotoxic murine monoclonal antibodies that recognize myeloid-specific antigens have been produced by immunization with normal human neutrophils or myeloblasts from a patient with acute myelomonocytic leukemia. Two of these, PMN 6 and PMN 29, are specific for neutrophils; the third monoclonal antibody, AML-2-23, is reactive with the majority of normal monocytes as well as a subpopulation of mature neutrophils. Although neutrophils from all individuals tested expressed these antigens, cytofluorographic analysis revealed that the percentage of cells bearing the PMN 6 and AML-2-23 antigens varied among individuals. Significant additional heterogeneity in the density of each antigen among antigen-bearing cells was also observed. All three antibodies efficiently mediated complement-dependent cytotoxicity of acute myelocytic leukemia cells yet were unreactive with lymphocytic leukemia cells. Neutrophil cytotoxicity was mediated by PMN 6 and PMN 29 but not by AML-2-23. On the other hand, AML-2-23, but not PMN 6 or PMN 29, was cytotoxic for normal monocytes and macrophages. These monoclonal antibodies may be of value in the study of normal neutrophil function and differentiation and may have clinical utility in diagnosis and therapy of myeloid leukemia.

Animals↗
PubMed1982

Studies on the ability of monoclonal antibodies to selectively mediate complement-dependent cytotoxicity of human myelogenous leukemia blast cells.

A panel of monoclonal antibodies that bind to leukemic blast cells from patients with acute myelocytic leukemia and chronic myelocytic leukemia in blast crisis was studied for their ability to mediate complement-dependent lysis of a variety of cell populations from patients with leukemia, normal blood cells, and human leukemia cell lines. Several of these monoclonal antibodies were selectively cytotoxic to myeloid leukemia cells (AML-1-99, AML-1-211, AML-2-30, CML-75, CML-115, and CML-150). Although they were all capable of binding to normal cell populations, none of these hybridomas were cytotoxic to normal cells. Three of these antibodies (AML-1-211. CML-75, and CML-150) were cytotoxic to some leukemia cell samples only after dilution of the hybridoma supernatant, i.e., they showed a prozone. Binding of these three antibodies, as well as another, AML-1-201, as determined in a radioimmunoassay, also showed a prozone. Other monoclonal antibodies are described (AML-2-23 and AML-2-9) that mediate complement-dependent cytotoxicity to myeloid leukemia cells as well as selected normal cell types (monocytes and lymphocytes, respectively). The potential clinical utility of these monoclonal antibodies is considered in the context of recently encountered problems in the use of monoclonal antibodies to mediate leukemia cell lysis in vivo.

Animals↗
PubMed1982

Monoclonal antibodies reactive with human myeloid leukaemia cells.

Hybridomas producing monoclonal antibodies that bind to determinants on myelogenous leukaemia blast cells were developed using fresh leukaemia blasts as immunogens. These monoclonal antibodies were used to quantitate the amount of a variety of antigens on both leukaemia and normal blood cells in a radioimmunoassay. The ability of these antibodies to mediate complement-dependent lysis of leukaemia cells and normal blood cells was evaluated. Significant quantitative differences in the expression of a variety of cell surface antigens were observed among different myeloid leukaemia cell samples, normal cells, and other forms of leukaemia. However, none of the monoclonal antibodies studied were found to be specific for myeloblasts. Despite the fact that these antibodies bound to both leukaemia and normal cells, several of them mediated complement-dependent cytotoxicity which was restricted to leukaemic myeloblasts (AML-1-211, AML-2-30, CML-18, CML-75, CML-115, and CML-150). None of these clones, alone or in any combination, were capable of lysing normal lymphocytes or monocytes. Others were specifically cytotoxic to leukaemia cell lines (AML-1-99), B cells and some leukaemia samples (AML-2-9), and myelomonocytic leukaemia cell samples and normal monocytes (AML-2-23). Several of the monoclonal antibodies from this panel appear to be promising for future clinical applications.

Antibodies, Monoclonal↗
PubMed1980

Thrombotic thrombocytopenic purpura: combined treatment with plasmapheresis and antiplatelet agents.

Seven of eight patients with thrombotic thrombocytopenic purpura who were treated with both exchange plasmapheresis and antiplatelet agents (aspirin and dipyridamole) achieved complete remission. The eighth patient appeared to fail on this regimen but responded to corticosteroids and splenectomy. A ninth patient attained full remission after therapy with only aspirin and dipyridamole. The antiplatelet agents appeared to play an important role in the response of four patients. Eight patients received maintenance aspirin and dipyridamole. This maintenance therapy may have prevented relapses of thrombotic thrombocytopenic purpura in some patients as evidence of active, subclinical disease persisted for many weeks in most patients. Treatment with maintenance antiplatelet agents was discontinued in five patients after 7 to 18 months and no patient has relapsed. An effective therapeutic regimen for thrombotic throbocytopenic purpura would include initial therapy with exchange plasmapheresis, aspirin, and dipyridamole and maintenance therapy with antiplatelet agents.

Adult↗
PubMedDate not supplied

Reversal of graft-versus-host disease with infusion of autologous bone marrow.

Graft-versus-host disease (GVHD) remains a major complication of bone marrow transplantation. This report describes reversal of GVHD by infusion of stored recipient bone marrow following combined liver-bone marrow allotransplantation. Graft-versus-host disease developed at the end of the first postoperative week. The skin involvement progressively spread to approximately 80% of the body surface and was not affected by modification of the immunosuppressive treatment. On the 42nd and 43rd postoperative day 1.23 x 10(8) and 1.6 x 10(8) autologous bone marrow cells per kg of recipient body weight were infused. The skin rush began to dramatically improve and resolved within 2 wk from the autologous marrow infusion. Autologous bone marrow storage previous to allogeneic bone marrow transplantation for tolerance induction could constitute a safety net in case of occurrence of GVHD.

Biopsy↗