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 incubation of K-562 leukemia cells with specific goat immunoglobulin resulted in gradual cytolysis in the absence of complement and effector cells. Optimal lysis (100%), reached in 3-4 days, occurred when the concentration of the antibody in the culture medium was about 20 micrograms/ml containing an initial inoculum of 15,000 cells. A lower concentration (10 micrograms/15,000 cells/ml) led to partial cytolysis; the surviving cells, cultured in fresh medium, were still vulnerable to antibody lysis (30 micrograms/ml), thus indicating the lack of an apparent resistant cell population. The amount of free antibody in the culture medium diminished rapidly and very little or none was detectable after 2-3 hours of incubation with K-562 cells. The immune gamma-globulin also inhibited colony formation of K-562 cells in soft agar. The immune gamma-globulin, absorbed extensively with normal blood cells, to pluripotent K-562 cells, cross-reacted with several human malignant hematopoietic cell lines tested. These cells included T-lymphoblasts (JM and MOLT-4), promyelocytes (HL-60), Burkitt's lymphoma cells (RAJI), myeloblasts (KG-1 and KG-1a), and multiple myeloma cells (K-737). The absorption of the immune gamma-globulin with an equal number of cells from each of the cell lines assayed diminished but did not completely remove the antibody responsible for cytolysis of K-562 target cells. Thus, the K-562 leukemia blasts appear to possess common and specific antigens that may be only partially expressed on other committed leukemia cell lines studied. For this reason, the cytolytic activity of the immune gamma-globulin could only be removed by absorption with K-562 cells possessing a complete array of antigens solely present on pluripotential hematopoietic cells.
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PMID:Antibody lysis of human hematopoietic cells in the absence of complement and effector cells. 618 38

A murine monoclonal antibody (OKT9) raised against human leukemic cells binds to a wide variety of leukemia and tumor cell lines and to a minority of leukemia cells taken directly from patients. Fetal thymus and liver are strongly reactive as are some normal, immature hemopoietic cells and activated lymphocytes. Reactivity with OKT9 appears to correlate with proliferation status in both normal and malignant populations. Biochemical analysis indicates that this structure is a approximately equal to 180,000-dalton glycoprotein with two disulfide-bonded subunits of approximately equal to 90,000-daltons. Isolation of the transferrin receptor from a T-cell line (MOLT-4) indicates that it also has a dimeric approximately equal to 180,000-dalton structure. Radio-labeled transferrin bound to its receptors can be specifically precipitated by the monoclonal OKT9, although the latter does not bind transferrin itself, indicating that the antigenic structure defined by this antibody is likely to be the transferrin receptor.
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PMID:Ubiquitous cell-surface glycoprotein on tumor cells is proliferation-associated receptor for transferrin. 627 Jun 80

The analysis of seven differentiation markers following incubation with the tumor promotor 12-O-tetradecanoylphorbol-13-acetate (TPA) was examined in the human leukemic T-cell line MOLT-3. Significant changes were observed in the activity of the markers terminal deoxynucleotidyl transferase (TdT). spontaneous proliferation and the ability of these cells to bind sheep erythrocytes. Levels of human thymus-leukemia-associated antigen (HThy-L) recently identified as a low molecular weight form of adenosine deaminase (ADA), were reduced by about 50%. No significant changes were observed in ecto-5'-nucleotidase [5'-NT) activities, in the proliferative response to PHA, or in the expression of IA-like antigens. These data and the time kinetics of the changes suggest that following incubation of these T-lymphoblasts with TPA there is a sequential loss of TdT, loss of the capacity for spontaneous proliferation, and the appearance of receptors for sheep erythrocytes. Subsequently there is a decrease in the level of HThy-L/ADA. This sequence appears to follow that proposed for prethymic precursor T-cell differentiation following activation with thymic epithelium.
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PMID:Modulation of human T-cell differentiation markers by 12-O-tetradecanoylphorbol-13-acetate. 627 66

Lithium is known to cause leucocytosis in normal humans, and lithium salts have been used therapeutically in attenuating leucopenia in patients undergoing chemotherapy. Recent reports also described leukaemia development during lithium treatment. We have investigated the effect of lithium chloride on the proliferation of human myeloid, erythroblastic, and T- and B-lymphoblast leukaemia cells in vitro. Colony formation by cells of the myeloid leukaemia lines HL-60 and KG-1 was enhanced by lithium chloride, and maximal stimulation was seen at 5 X 10(-4) M. Lithium also increased the proliferation of KG-1a cells, a subline of KG-1 cells that does not respond to colony-stimulating factor, indicating a direct growth-promoting effect on myeloid leukaemia cells. Lithium was found to enhance colony formation by the T-lymphoblast cell line MOLT 4 and the B-lymphoblast line IM-9 at concentrations between 10(-6) and 10(-3) M. The addition of lithium chloride to murine Friend or human K-562 erythroleukaemia cells also caused an augmentation in colony formation. These observations may have relevance to the therapeutic use of lithium in patients with haematological malignancies.
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PMID:Lithium enhances growth of human leukaemia cells in vitro. 628 51

Natural killer cell activity was evaluated in children with acute lymphocytic and acute myelogenous leukemia. Peripheral blood mononuclear cells isolated at the time of diagnosis and before initiation of therapy were mixed with 51Cr-labeled K562 or MOLT-4 target cells at a ratio of 100:1. In 13 consecutive cases of acute lymphocytic leukemia, the mean percentage of lysis of K562 cells (15.0%) was significantly below that of adult (49.8%) and age-related controls (35.9%). A similar pattern was observed against MOLT-4 targets (acute lymphocytic leukemia, 11.3%; adults, 39.8%; and pediatric controls, 28.4%). The mean activity in 8 cases of acute myelogenous leukemia was also markedly reduced (6.8% versus K562 and 6.0% versus MOLT-4). Linear regression analyses of white blood cell, lymphocyte, and leukemia blast counts failed to demonstrate any correlation between peripheral cell counts and natural killer cell activity. Thus, it would not appear that the observed decrease in lysis was due merely to dilution of effectors with blasts. The lytic activity of cells isolated from patient blood was significantly lower than that from cells isolated from an equal volume of blood from a normal adult. These results suggest that the decreased natural killer cell activity is not explained by simple dilution. Instead, they indicate an absolute decrease in lytic potential. Additional experiments have precluded suppressor cell involvement and competitive inhibition of blasts with target cells as possible causes for depressed lysis.
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PMID:Decreased natural killer cell activity in children with untreated acute leukemia. 635 19

Two anti-Mr 65,000 protein (p65) murine monoclonal antibodies, T101 and VIII-1, were conjugated to intact ricin. Toxicity of the resulting immunotoxins (IT) was measured against leukemic cell lines treated alone and in the presence of excess bone marrow using a highly sensitive colony inhibition assay. Cells were pretreated with IT in the presence of lactose to block the native binding of ricin. The IT proved to be potent cytotoxins for the p65-positive cell lines, CEM and MOLT-4. Treatment with T101-ricin (1000 ng/ml) inhibited clonogenic activity of these lines by more than 5.1 logs. Less than 1 log of the inhibition at this dose was due to nonspecific killing by IT. Notably, the presence of excess bone marrow did not reduce IT toxicity against the leukemic populations. Comparison of IT concentrations which inhibited 50% of clonogenic activity showed that T101-ricin was 140- to 540-fold and VIII-1-ricin was 12- to 192-fold more toxic to p65-positive than to p65-negative cell lines. Neither unconjugated anti-p65 nor IT prepared with an irrelevant antibody inhibited clonogenic activity. Blocking of IT toxicity by unconjugated antibody further demonstrated that the antibody moiety of the IT directed the selective toxicity. We found that T101-ricin was more toxic for CEM cells than was VIII-1-ricin, even though blocking studies indicated that the two antibodies bind to proximal or identical epitopes. This report is unique in that an IT was shown to specifically eliminate greater than 99.99% of leukemic cells from human bone marrow. These findings indicate the utility of T101-ricin as an in vitro reagent for autologous bone marrow transplantation in treatment of T-cell leukemia.
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PMID:Elimination of clonogenic T-leukemic cells from human bone marrow using anti-Mr 65,000 protein immunotoxins. 637 99

The human T-cell leukaemia and differentiation antigen HTA 1 is defined by the monoclonal antibody NA1/34 (ref. 1) and also recognized by the monoclonal antibody OKT6. Like class I products of the human major histocompatibility complex, it has a glycosylated heavy (alpha) chain of approximately 45-50,000 molecular weight (MW) in non-covalent association with beta 2-microglobulin (beta 2m) (MW 11,900). A particular feature of HTA 1 is the presence in significant amounts of an additional beta 2m-like subunit, called beta t (refs 3, 4). Top facilitate biochemical studies we have prepared a high HTA 1 expressor variant (NH17) of the human thymoma line MOLT-4. The N-terminal amino acid sequence of the beta t purified from this cell line was shown to be indistinguishable from that of bovine beta 2m. Further, beta t was present when the cells were grown in medium containing fetal calf serum (FCS), but absent from cells grown with human serum (HuS). We show here that addition of human and bovine beta 2m to MOLT-4 and NH17 cells grown in serum-free medium produces a significant elevation of HTA 1 antigen expression, providing evidence for a regulatory or stabilizing function for the exchange of extracellular beta 2m with a cell-surface antigen.
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PMID:Serum beta 2-microglobulin binds to a T-cell differentiation antigen and increases its expression. 642 30

Allogeneic lymphocytes can stimulate cell-mediated cytotoxicity (CMC) in lymphocytes from leukaemia patients against autologous leukaemia target cells. We have compared the capacity of different allogeneic lymphoid cells to stimulate CMC to fresh (i.e., patient) and cultured (MOLT 4, K562) leukaemic target cells in lymphocytes from an acute leukaemic patient and his HLA-identical siblings. Allogeneic lymphoid cells, and particularly a lymphoblastoid cell line, were effective in stimulating CMC to leukaemia targets. In some instances, however, leukaemia cells derived from the patient, mixed with allogeneic lymphoid cells stimulated synergistic CMC to the patient's leukaemia. We also found that the patient's leukaemia cells alone were able to stimulate CMC in HLA-identical sib lymphocytes to fresh and cultured leukaemia targets. Extra specificities on fresh leukaemia cells were revealed when these cells induced unpredicted CMC on normal lymphocyte targets when added to mixed lymphocyte cultures (MLC) between related and unrelated lymphocytes. Cytotoxic lymphocytes generated in MLC against the patient's HLA antigens were absorbed by monolayers of lymphocytes and leukaemia cells of the same HLA type as the patient, leaving residual CMC to fresh (patient) and cultured (K562) leukaemia target cells. In addition, CMC to the patient's leukaemia cells, stimulated in lymphocytes from the patient's HLA-identical sib by allogeneic cells, was absorbed by a monolayer of these allogeneic cells. This suggests cross reactivity between determinants on the leukaemia and allogeneic lymphocytes. The results of this study are consistent with expression of 'leukaemia antigen', which are not restricted to leukaemia cells but may also be expressed on lymphocytes.
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PMID:The role of allogeneic cells in the stimulation of cell-mediated cytotoxicity to leukaemia cells. A family study. 655 6

We have generated and characterized a hybridoma monoclonal antibody, termed SN1, that defines a unique human T-cell leukemia antigen. This antibody was generated by using a human leukemia antigen preparation isolated from cell membranes of MOLT-4, a leukemia T-cell line derived from a patient with T-cell-type acute lymphoblastic leukemia (T-ALL). SN1 was characterized by a sensitive microscale radioimmunoassay using a variety of cultured and uncultured human cells. In selected cases, the cell specimens were further tested by immunoperoxidase staining and an immunofluorescence staining test. The results of the radioimmunoassay were in agreement with those of the two other tests. Among the various cultured malignant and nonmalignant cell lines, SN1 reacted only with leukemia T-cell lines derived from patients with T-ALL; it reacted with all six T-ALL cell lines tested-i.e., JM, CCRF-CEM, CCRF-H-SB2, RPMI 8402, PEER, and MOLT-4. In the case of uncultured cell specimens derived from cancer patients, SN1 reacted with four of four cases of T-ALL but did not react with specimens derived from 41 patients with other types of cancer. SN1 did not react with any normal human cell specimens tested, both cultured and uncultured. These specimens include normal lymphoblastoid cell lines, thymocytes, bone marrow cells, spleen cells, lymph node cells, peripheral blood mononuclear cells, lymphocytes containing B and T cells, purified T cells, monocytes, granulocytes, erythrocytes, and platelets. Furthermore, SN1 did not react with phytohemagglutinin-activated T cells nor with concanavalin A-activated T cells. The results show that monoclonal antibody SN1 defines a type of human leukemia antigen that is expressed on the cell surface of T-cell-type ALL cells. The results further show the usefulness of SN1 in the diagnosis of cancer patients and suggest its therapeutic potential. We designate this antigen TALLA, a T-cell ALL antigen.
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PMID:Monoclonal antibody that defines a unique human T-cell leukemia antigen. 660 Aug 41

We generated a monoclonal antibody, termed SN2, which defines a human T cell leukemia-associated cell surface glycoprotein, GP37, with an approximate m.w. of 37,000. This antibody was generated by using a human leukemia antigen preparation. The reactivity and specificity of SN2 were characterized by a sensitive radioimmunoassay against a variety of cultured and uncultured human cells. In selected cases, the cell specimens were tested further by indirect immunofluorescence staining. Among the various cultured malignant and nonmalignant human cell lines tested, SN2 reacted only with leukemic T cell lines, with one exception. It reacted with 10 of 11 leukemic T cell lines tested; the 10 reactive cell lines are PEER, JM, MOLT-4, CCRF-CEM, CCRF-H-SB2, RPMI 8402, DND-41, HPB-ALL, SKW-3, and HPB-MLT; the unreactive line was HUT 78. The reactive cell lines were derived from patients either with T cell-type acute lymphoblastic leukemia (the first eight cell lines), with T cell chronic lymphocytic leukemia (SKW-3), or with Japanese adult T cell leukemia-lymphoma (HPB-MLT). The unreactive cell line, HUT 78, was from a patient with Sezary syndrome. Results consistent with the above were obtained from studies in which uncultured malignant cell specimens from different cancer patients were tested against SN2; SN2 reacted only with T leukemia cells. Among various uncultured normal cell specimens tested, SN2 did not react with thymocytes, bone marrow cells, peripheral blood lymphocytes containing B and T cells, purified T cells, monocytes, granulocytes, or erythrocytes. It did, however, react with platelets.
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PMID:Monoclonal antibody SN2 defining a human T cell leukemia-associated cell surface glycoprotein. 660 54


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