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)

A monoclonal antibody, M241, was produced which binds to a human cell surface molecule with properties similar to the murine thymus leukemia (TL) antigen. This human TL-like antigen was found on thymocytes and some T cell lines derived from patients with acute lymphocytic leukemia, but was not found on peripheral blood lymphocytes or B cell lines. The monoclonal antibody M241 was used to immunoprecipitate a molecule from lysates of 125I surface-labeled MOLT 4 cells which had two subunits, a 43-kDa chain and a 12-kDa chain. The small subunit was shown to be beta 2-microglobulin (beta 2m) by immunoprecipitation with a monoclonal antibody, BBM.1, which recognizes human beta 2 m. The TL-like molecule recognized by M241 was shown to be serologically distinct from the HLA-A,B,C molecules recognized by three monoclonal antibodies W6/32, PA2.6 and BB7.8, and distinct from another human thymocyte antigen, the 49 kDa HTA 1 molecule, recognized by the monoclonal antibody NA1/34. Following removal of the HLA-A,B,C molecules, the HTA 1 molecules, and the M241-defined TL-like molecules from MOLT 4 lysates, additional beta 2m-associated molecules were immunoprecipitated with BBM.1. These molecules contained a 45-kDa subunit attached to beta 2m.
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PMID:A monoclonal antibody recognizing a human thymus leukemia-like antigen associated with beta 2-microglobulin. 675 87

We have identified previously a quantitatively minor membrane protein (p28) with an apparent reduced m.w. of 28,000, which is biosynthetically labeled in activated human lymphocytes. Rabbit antisera with activity directed against p28 (alpha-ATC) were prepared and p28 was identified by immunoprecipitation in NP-40 extracts of activated, extrinsically labeled lymphocytes. p28 was not expressed in appreciable amounts by unstimulated T cells, stimulated or unstimulated B cells, null cells, or adherent cells. Protein p28 was only minimally represented on resting thymocytes but was easily detected on 4-hr activated thymocytes and the T lymphoblastoid cell lines HSB2 and MOLT-4. Absorption and immunoprecipitation studies with alpha-ATC indicated that p28 was not present on erythrocytes, platelets, neutrophils, six B cell lines, six null cell lines, and seven other T lymphoblastoid cell lines. Protein p28 from HSB2 cells was absorbed by lentil lectin, concanavalin A, and wheat germ agglutinin affinity columns and was eluted with the appropriate sugars. Gel filtration column chromatography of unreduced p28 in the presence of 0.5% NP-40 or 0.1% deoxycholate gave elution characteristics consistent with a m.w. of approximately 60,000 to 100,000. In preparative isoelectric focusing (IEF) studies the isoelectric point (pI (p28) = 5.2 to 6.1) was similar or identical to that described for the reduced and denatured protein in two-dimensional polyacrylamide gels (pI = 5.5 to 6.2). Protein p28 was eluted from DEAE-cellulose (Whatman DE-52) ion exchange columns at 0.05 to 0.15 M NaCl. Experiments with monoclonal antibodies or heteroantisera specific for other T cell and B cell antigens and various lymphoblastoid cell lines and normal peripheral blood cells indicated that p28 is distinct from the human Ia-like antigens, from T3, T4, T5, T8, and from several other reported human T cell antigens that appear to correspond to Thy-1, the sheep erythrocyte receptor, and a human thymus-leukemia antigen.
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PMID:Properties of a surface antigen expressed on activated human thymus-derived lymphocytes. 680 Nov 23

Terminal deoxynucleotidyl transferase was purified to homogeneity from the blasts of eight patients with leukemia and compared with purified transferase from normal human and calf thymus. In two cases phenylmethanesulfonylfluoride was added during purification to reduce proteolysis. Comparative kinetic analyses of the purified enzymes indicated no differences in catalytic properties. There was substantial variation in the molecular structure of terminal transferase on denaturing polyacrylamide gels: (a) a protein that migrated as a single polypeptide with M(r) = 62,000 was isolated from two patients with acute lymphoblastic leukemia and from MOLT-4 cells; (b) a protein that migrated as a single polypeptide with M(r) = 42,500 was isolated from two patients with acute lymphoblastic leukemia; (c) a protein that migrated as a single polypeptide with M(r) = 42,500 was isolated from two patients with chronic myelogenous leukemia in blast crisis; (d) a protein that migrated as two non-identical subunits of M(r) = 27,000 and 10,000, respectively, was isolated from two additional patients with chronic myelogenous leukemia in blast crisis. The subunit structure of d is characteristic of the homogeneous enzymes purified from human and calf thymus. Neutralizing and precipitating antibodies to terminal transferase from human lymphoblasts and calf thymus have been produced in rabbits and goats. Antisera directed against either human or calf antigens neutralize enzymatic activity and precipitate all forms of human terminal transferase. The multiple human forms give reactions of antigenic identity by immunodiffusion, but differ antigenically from the calf enzyme. The multiple forms of terminal transferase could represent physiological processing, artifactual degradation, or isozymes coded by several genes.
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PMID:Biochemical and immunological properties of human terminal deoxynucleotidyl transferase purified from blasts of acute lymphoblastic and chronic myelogenous leukemia. 693 74

Conditions were determined for successful subcutaneous tumor development of MOLT-4 human T-cell leukemia cells in BALB/c nude (nu/nu) female mice. MOLT-4 cells injected alone at one site resulted in tumors in none of 21 mice, whereas MOLT-4 cells injected with X-irradiated human fibrosarcoma cells (HT-1080) at another site resulted in tumors in 5 of 21 mice. When X-irradiated three times with 200 rad over a 3-week period and then inoculated with MOLT-4 cells and X-irradiated HT-1080 cells, 19 of 25 mice developed tumors, which indicated that a combination of X-irradiation of the recipients and inoculation of an admixture of the leukemia cells with X-irradiated fibrosarcoma cells markedly increases tumor incidence. The cells growing in the tumors had the characteristics of MOLT-4, as assessed by marker studies and histology.
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PMID:Successful transplantation of a human leukemia cell line into nude mice: conditions optimizing graft acceptance. 694 23

To determine whether vindesine receptors are present in human leukaemic cells, K562 cells (established from chronic myelogenous leukaemia in blastic crisis) were incubated with 3H-vindesine. Binding of 3H-vindesine increased with incubation time and with increase in number of K562 cells. However, when excessive amounts of nonradioactive vindesine were added, the 3H-vindesine was displaced. Binding of 3H-vindesine was only inhibited by vinblastine, vincristine and vindesine. These results suggest that K562 cells have receptors for vindesine and that these receptors are common to vinca alkaloids. Scatchard analysis showed that the number of vindesine receptors differed according to the kind of cells tested. K562 and a T-cell leukaemia-derived cell line, MOLT-4, had more receptors than an acute promyelocytic leukaemia-derived cell line, HL-60, and normal blood lymphocytes. The degree of vindesine affinity to receptors did not differ markedly among the above-mentioned cells.
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PMID:Vindesine receptors in cells of a human leukaemia cell line. 695 39

Two monkey antisera against human thymocytes after absorption with human erythrocytes and peripheral blood leukocytes were shown to detect human thymus-leukemia (HTL)-like antigens. These sera were cytotoxic for thymocytes (> 90% lysis at a 1:10 dilution) but were nonreactive with enriched peripheral blood T- and B-lymphocytes or with cells from myeloid or B-cell lymphoid leukemias. Most (16/17) sheep erythrocyte rosette-forming acute lymphoblastic leukemia (ALL) cells reacted with these sera. Cells from patients with T-cell chronic lymphocytic leukemia, lymphoblastic lymphoma (LBL), and thymoma were also positive. Three of 4 T-cell lymphoblastoid lines derived from ALL patients reacted with these sera. Absorption of the sera with MOLT-4F cells, thymocytes, or LBL cells removed the reactivity against all types of cells tested. However, sera absorbed with the T-cell line HSB remained cytotoxic for thymocytes, MOLT-4F, and most (6/9) T-cell cancers tested. The peripheral blood cell-absorbed sera precipitated a molecule with an apparent molecular weight of 48,000 from lactoperoxidase-labeled thymocytes but not from similarly labeled peripheral blood lymphocytes. The ability of the sera to precipitate this antigen was decreased by absorption with thymocytes, MOLT-4, or LBL cells but not by absorption with HSB, SB, or non-T, non-B ALL cells. Sequential precipitation studies suggested that the HTL antigen was not associated with beta 2 microglobulin.
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PMID:Detection and partial characterization of human thymus-leukemia antigens. 696 69

The antigenic properties of leukaemic cells from five patients with adult T cell leukaemia were studied with rabbit anti-MOLT-4 and anti-human thymocyte antisera using indirect membrane immunofluorescent staining. The E rosette-positive, surface immunoglobulin (sIg) negative leukaemic cells from these patients gave a positive reaction with the appropriately absorbed antisera, which reacted specifically with thymocytes, cells from T cell acute lymphoblastic leukaemia (T-ALL) and T-ALL-derived lymphoblastoid cell lines (T-LCLs) and normal peripheral blood T cells. Nevertheless, the antisera further absorbed with fresh normal peripheral blood lymphocytes (FN-PBL) lost almost all the reactivities with the leukaemic cells as well as with normal peripheral blood T cells but still retained the reactivities with thymocytes, T-LCLs and T-ALL cells. The results suggest that adult T cell leukaemia cells possess a peripheral blood T cell antigen but not a thymocyte-specific antigen.
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PMID:Immunological distinction of adult T cell leukaemia from T cell acute lymphoblastic leukaemia. 696 47

The purpose of this paper was to study the heterogeneity of human thymocytes and leukemic cells of the T-cell line MOLT-3 by velocity sedimentation. Analysis of the subpopulations of thymocytes demonstrated that they represent a heterogeneous population of cells with respect to their size, proliferative activity, and presence and quantities of terminal deoxynucleotidyl transferase and human thymus leukemia-associated antigen, a thymic isozyme of adenosine deaminase (HThy-L/ADA). Only a minor subpopulation of thymocytes (large cells) was in active cycle. The highest level of HThy-L/ADA was associated with the main subpopulation of thymocytes sedimenting at 3 to 4 mm/hr while low amounts of the HThy-L/ADA antigen (enzyme) were found in the minor fractions of the small and large cells. The distribution of terminal deoxynucleotidyl transferase-positive cells indicated that most, but not all, thymocytes contain the enzyme. Analysis of the T-cell line MOLT-3 showed that these cells could be separated into subpopulations with different biochemical and biological properties. More than one subpopulation of cells was capable of DNA synthesis. In contrast to the thymocytes, all fractions of MOLT-3 cells contained high amounts of HThy-L/ADA. The proportion of terminal deoxynucleotidyl transferase-positive cells as a function of sedimentation velocity was also quite constant although there was a slight but reproducible drop in the percentage of these cells in the slowly sedimenting fractions. The percentage of cells with receptors for sheep erythrocytes also remained high in fractions separated on the basis of size, although a consistently higher percentage was found in smaller cells. These studies indicated that thymus cells as well as the malignant T-cell line MOLT-3 can be separated on the basis of sedimentation velocity into subpopulations with different biological and biochemical properties. The data also indicated that the heterogeneity of MOLT-3 line cannot be explained solely on the basis of volume changes due to cell cycle, suggesting that they may represent heterogeneous populations of cells.
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PMID:Heterogeneity of human thymocytes and a malignant T-lymphoblast cell line, MOLT-3. 697 Nov 48

Two rabbits immunized with 15 micrograms of a purified human thymus leukemia-associated antigen preparation and boosted once with the same amount of the antigen preparation yielded antisera that showed strong specificity for human leukemic T-cells without any prior absorptions. These antisera from the two rabbits showed a 50% killing of cells at antiserum dilutions of 5700- and 1600-fold, respectively, against JM, a leukemic T-cell line, and slightly weaker activity against MOLT-4, another leukemia T-cell line. These antisera, without any absorption, showed no or minimal reaction against two nonmalignant B-cell lines (RPMI 1788 and RPMI 8057), a leukemic non-T, non-B-cell line (NALM-16), a leukemic pre-B-cell line (NALM-1), normal peripheral blood lymphocytes, and T-cells isolated from peripheral blood lymphocytes. Antiserum 7557, which showed the higher antibody activity, was further studied by an absorption test using various human cell lines. The antiserum showed strong activity against all three leukemic T-cell lines tested, i.e., CCRF-CEM, RPMI 8402, and CCRF-HSB-2, whereas it showed no significant activity against other cell lines which included two leukemic non-T, non-B-cell lines (KM-3 and NALM-6), NALM-1 and RPMI 1788. These are the first anti-human leukemia antisera, except for monoclonal hybridoma antibodies, that showed good specificity for leukemia cells without prior absorption. The present procedure of immunizing animals with a small amount of human thymus leukemia-associated antigen preparation isolated from cell membrane will also be useful for obtaining strong, specific antisera of other cell membrane antigens.
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PMID:Strong, specific anti-human leukemia antisera prepared with the use of purified cell membrane antigen. 697 2

D-Mannosamine is toxic to human malignant T-lymphoid cell lines derived from patients with T-cell leukemia. We observed heterogeneity of mannosamine susceptibility among those cell lines. The leukemic T-cell lines, subgrouped according to the degree of mannosamine inhibition on nucleic acid biosyntheses, were: Subgroup 1, HPB-MLT cells; Subgroup 2, CCRF-HSB-2 and HPB-ALL cells; and Subgroup 3, MOLT-4 cells. The most sensitive line, HPB-MLT, originated from the patient with adult T-cell leukemia. The cytotoxicity of mannosamine was potentiated by a fatty acid, sodium oleate, at concentrations that were noncytolytic, and the interaction between the two drugs was synergistic. These results would suggest that mannosamine induces changes in the membrane structure of the leukemia cells. Thus, the primary target of the tumoricidal activity of mannosamine may also be the cellular membranes.
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PMID:Antitumor activity of D-mannosamine in vitro: different sensitivities among human leukemia cell lines possessing T-cell properties. 697 85


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