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 possible presence of tumor cells in remission bone marrow (BM) is one of the major problems for the success of autologous BM transplantation (ABMT), because the reinfusion of viable malignant cells may result in relapse. In this study we attempted the purging of the malignant cells by the use of VP-16-213 (VP-16) and nitrogen mustard (NM) either alone or in combination. Four cell lines from various hematological malignancies were utilized: SK-DHL-2 was established from a B-cell diffuse histiocytic lymphoma; RAJI was from an Epstein-Barr virus (EBV)-infected B-cell lymphoma cell line; K-562 were from a chronic myelogenous leukemia (CML) blastic crisis; and HL-60, derived from a human promyelocytic leukemia, were used in exponential growth phase. Four logs of tumor cell-elimination were observed after 1-h incubation of RAJI cells with 25 micrograms/ml of VP-16. K-562 and SK-DHL-2 cells showed a greater than 4 logs reduction after 1-h exposure to 75 micrograms/ml of VP-16, and HL-60 cell line growth was inhibited by 3.2 logs. Under the same conditions (i.e., the treatment with 75 micrograms/ml), we observed a mean recovery of 2.7% of BM granulocyte-macrophage colonies (granulocyte-macrophage colony-forming units, CFU-GM), 3.2% of erythroid (erythroid burst-forming units, BFU-E), and 2.5% of pluripotent (granulocyte erythrocyte macrophage megakaryocyte colony-forming units, CFU-GEMM) progenitors, respectively. More than 3 logs reduction of leukemia and lymphoma cell lines were reached following 1-h treatment with 1 micrograms/ml of NM. After exposure to the same concentration of the drug we obtained 2.5% CFU-GM, 1.2% BFU-E, and 2% CFU-GEMM recovery. A drug mixture containing constant doses of VP-16 (10 and 20 micrograms/ml) and NM (1 micrograms/ml) reduced HL-60 and SK-DHL-2 cell growth to undetectable levels (i.e., 4 and 5 logs elimination) in the presence of an excess of irradiated BM cells, whereas it did not further affect the recovery of the BM precursors as compared to the single drugs used alone. These results suggest that the combination of these two drugs at the selected dose level could provide a better therapeutic index (i.e., higher tumor cell killing coupled with no additional cytotoxic effect on normal BM cells) than the same chemotherapeutic agent used alone and that this mixture may be useful for the "ex vivo" treatment of BM grafts.
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PMID:In vitro cytotoxicity of VP-16-213 and nitrogen mustard: agonistic on tumor cells but not on normal human bone marrow progenitors. 239 48

Blood lymphocytes from 50 patients with chronic B-lymphocytic leukaemia (B-CLL) were cultured in vitro with and without the polyclonal B-cell activators (PBA) dextran sulphate (DxS), lipopolysaccharide from E. coli (LPS), and Epstein Barr virus (EBV). Patients with blood lymphocytes that showed a high spontaneous or PBA-induced 3H-thymidine uptake in 4 d cultures had a significantly shorter therapy-free survival than patients whose lymphocytes showed a low thymidine uptake. The DxS-induced cellular thymidine uptake was the most powerful predictor of prognosis. Eighteen patients with leukaemic cells responding to DxS stimulation had a median therapy-free survival of 17 months and a probability of 5 year therapy-free survival of less than 0.1, whereas for 30 patients with DxS unresponsive cells the corresponding figures were greater than 120 months and greater than 0.7, respectively (log rank, P less than 0.0001). A multivariate Cox's regression analysis revealed that the DxS-induced leukaemic cell response was of greater prognostic importance than clinical features such as blood counts and staging according to Rai and Binet. Therefore PBA-induced leukaemic cell thymidine uptake seems valuable in the prediction of prognosis in B-CLL.
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PMID:Prognostic value of B-cell mitogen-induced and spontaneous thymidine uptake in vitro in chronic B-lymphocytic leukaemia cells. 241 8

A hairy cell leukemia cell line designated "Hair-M" was established in a suspension culture derived from the peripheral blood of an 86-year-old Japanese male with a diagnosis of hairy cell leukemia. The Hair-M cells were identified as having prominent hair-like cytoplasmic projections by examination with phase-contrast and scanning electron microscopy. These cells displayed ruffled membranes and stublike microvilli similar to those observed on the surfaces of cells in the peripheral blood of the patient. Immunologic and cytochemical studies on the Hair-M cells confirmed derivation from the clone of the patient's leukemia cells. Although the cultured Hair-M cells had definite B-cell characteristics, such as IgG kappa-chains on the surface and in cytoplasm, they also demonstrated Tac antigen, which is usually expressed on activated T-cells, and myelomonocyte antigens determined by OKM-1 and MCS-1 monoclonal antibodies. Other cell surface markers, including E(-), IgGFc(-), IgMFc(-), C3R(+), Ia-like antigen(+), OKT9(+), OKT10(+), and terminal deoxynucleotidyl transferase(-), were detected; no Epstein-Barr virus-determined nuclear antigen was detected. The karyotype of the Hair-M cells was determined to be 46XY with -11, -14, and two marker chromosomes. The Hair-M cells also had phagocytic activity to rabbit anti-human IgG serum-coated polyacrylamide gel particles.
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PMID:Establishment of a hairy cell leukemia cell line carrying Tac antigen and phagocytic activity with B-cell characteristics. 241 46

We report the production and characterization of a human monoclonal antibody reactive against the major envelope glycoprotein of human T-cell leukemia virus type I (HTLV-I), a virus linked to the etiology of adult T-cell leukemia. We exposed lymph-node cells derived from a patient with adult T-cell leukemia to the Epstein-Barr virus in vitro and obtained a B-cell clone (designated 0.5 alpha) by a limiting dilution technique. The secreted product of 0.5 alpha is a monoclonal antibody (also designated 0.5 alpha; that is IgG1 and has kappa light chains) that binds to the cell membrane of T-cells infected with HTLV-I and lyses them in the presence of complement. The antibody does not react with HTLV-I-negative T cells. In electroblot assays, the monoclonal antibody detects a 46-kDa glycoprotein in disrupted HTLV-I virions and a 34-kDa product following digestion of the viral protein with endoglycosidase F. These molecules have been reported to represent the HTLV-I env gene products. The antibody does not react with HTLV-II and HTLV-III virions. Glycoproteins of 61 and 68 kDa, which are known to be encoded at least in part by the env gene of HTLV-I, are precipitated by the antibody from endogenously radiolabeled HTLV-I-infected HUT 102-B2 and MT-2 cells, respectively. These results suggest that this human monoclonal antibody reacts with an env-encoded glycoprotein of HTLV-I. By using a competition assay with a biotin-labeled 0.5 alpha antibody, we observed that 15 out of 15 patients with adult T-cell leukemia had antibodies that block binding of the 0.5 alpha antibody to HTLV-I virions. This suggests that the antigen detected by 0.5 alpha antibody is a common epitope recognized in HTLV-I-infected individuals in vivo. This antibody, as well as the general strategy for making human monoclonal antibodies reactive against pathogenic retroviruses, may have diagnostic or therapeutic application.
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PMID:Human monoclonal antibody directed against an envelope glycoprotein of human T-cell leukemia virus type I. 242 59

Three murine monoclonal antibodies, named 2H9, 1E9 and 1A2, were produced after immunization of BALB/c mice with cells of the SU-DHL-1 cell line from a true histiocytic lymphoma. In frozen sections from various lymphomas, 2H9 and 1A2 selectively stained the cell membranes of neoplastic cells in true histiocytic lymphoma and Hodgkin's disease. Antibody 1E9 stained the nuclear membranes of the tumor cells in true histiocytic lymphoma and malignant histiocytosis. No staining was seen in 56 cases of B and T cell lymphoma. Several tissue culture cell lines, including T cell acute lymphoblastic leukemia and pre-B cell lines, were not stained. With 2H9, however, a positive reaction was noted for two Epstein-Barr virus (EBV)-positive African Burkitt's lymphoma cell lines (Daudi and P3HRI), one human T cell lymphoma/leukemia-virus-positive cell line (HUT 102), and one EBV-transformed normal B lymphoblastoid cell line (RPMI 8057). In normal lymphoid tissues, 2H9 and 1E9 reacted with the nuclear membranes of histiocytes and interdigitating reticulum cells, whereas 1A2 stained only rare cells of an unknown type. All three antibodies failed to react with B or T cells in frozen tissue sections of normal lymphoid tissues. The use of these three antibodies should facilitate the diagnosis of histiocyte and interdigitating reticulum (IR) cell-related neoplasms, namely, true histiocytic lymphoma, malignant histiocytosis, and Hodgkin's disease. True histiocytic lymphoma and Hodgkin's disease exhibit similar reactivities with these three and with two other monoclonal antibodies (HeFi-1 and Tac), suggesting that these two types of lymphoma are related. In contrast, malignant histiocytosis was negative for 2H9, 1A2, Tac, and HeFi-1. The difference in the phenotypic expression of true histiocytic lymphoma and malignant histiocytosis indicates that they are two different disease entities.
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PMID:Monoclonal antibodies against SU-DHL-1 cells stain the neoplastic cells in true histiocytic lymphoma, malignant histiocytosis, and Hodgkin's disease. 242 24

A 3.0-kilobase-pair Epstein-Barr virus (EBV) DNA segment necessary for lymphocyte immortalization encodes at least part of a nuclear protein (EBNA2) which is characteristically expressed in latently infected, immortalized cells. A 1.5-kilobase open reading frame within this DNA segment has now been inserted into a murine leukemia virus (MuLV)-derived expression vector (pZIP-NEO-SV(X)1) which provides for transcription of heterologous DNA but not for translational start. Transfection of the recombinant DNA into NIH 3T3 cells resulted in expression of a full-sized EBNA2 which localized to the cell nucleus. Significant new evidence is thereby provided that this 1.5 kilobase open reading frame includes a translational start site and encodes the entire EBNA2 protein. Transfection of the recombinant DNA into a helper cell line (psi am22b) providing amphotropic MuLV-packaging functions resulted in the release of a recombinant MuLV carrying the EBNA2 gene. This recombinant virus can infect rodent cells and convert them to stable EBNA2 expression. Rat-1 cells infected with the MuLV EBNA2 recombinant expressed EBNA2 and grew more rapidly in medium supplemented with 1 or 0.5% fetal calf serum than did Rat-1 cells infected with MuLV vector lacking EBNA2. The Rat-1 cells expressing EBNA2 remained contact inhibited, anchorage dependent, and nontumorigenic in nude mice. Different EBV isolates have one of at least two EBNA2 alleles. Despite divergence between the two alleles, a human serum recognized the prototype EBNA2 allele (EBNA2A) as well as the variant EBNA2B allele characteristic of some Burkitt tumor EBV isolates. The EBNA2B allele was also expressed from the MuLV-derived vector. The reproducible expression of EBNA2A or EBNA2B from these recombinant vectors will facilitate analysis of the EBNA2A and EBNA2B phenotypes.
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PMID:Expression of the Epstein-Barr virus nuclear protein 2 in rodent cells. 242 68

Decay-accelerating factor (DAF) is one of a family of cell-associated proteins that undergo posttranslational modifications in which glycolipid anchoring structures are substituted for membrane-spanning sequences. The signals that direct the covalent substitution reaction in these proteins are unknown. Human DAF was expressed in Chinese hamster ovary (CHO) cells and murine BW lymphocytes. In both cases, the xenogeneic DAF in transfectants incorporated a glycolipid anchor. A chimeric CD8-DAF cDNA, encompassing the extra-cellular region of the T-lymphocyte surface antigen CD8 and the 3' end of DAF mRNA (encoding the C-terminal region of mature DAF as well as the hydrophobic extension peptide), was expressed in human leukemia lines after transfection with an Epstein-Barr virus-based episomal vector. The chimeric protein in transfectants demonstrated glycolipid anchoring, whereas unaltered CD8 in control experiments did not. The signals directing glycolipid anchoring in eukaryotic cells are thus evolutionarily conserved and contained in the 3' end of the DAF sequence.
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PMID:Glycolipid reanchoring of T-lymphocyte surface antigen CD8 using the 3' end sequence of decay-accelerating factor's mRNA. 245 63

Transcription from the Moloney murine leukemia virus (Mo-MuLV) long terminal repeat (LTR) is inhibited in murine stem cells and induced during maturation of these cells. We have investigated whether alterations in the activity of this viral regulatory element also occur during differentiation of human myeloid leukemia cells. The Mo-MuLV LTR and the simian virus 40 (SV40) early promoter were introduced into HL-60 promyelocytes on Epstein-Barr virus-derived chloramphenicol acetyltransferase expression vectors. When these cells were induced to terminally differentiate, transcription from the Mo-MuLV LTR was induced approximately 10-fold. Expression from the SV40 promoter remained constant during differentiation of these cells. Replacing the SV40 transcriptional enhancer with the Mo-MuLV LTR transcriptional enhancer rendered the SV40 promoter inducible during differentiation. We conclude that sequences within the transcriptional enhancer of the Mo-MuLV LTR contain cis-acting elements responsible for induction of gene expression during differentiation of human myeloid cells.
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PMID:Induced expression from the Moloney murine leukemia virus long terminal repeat during differentiation of human myeloid cells is mediated through its transcriptional enhancer. 247 90

Two monoclonal antibodies (mAb) 1D1 and 2A6 were obtained from a fusion following hyperimmunization with prolymphocytic leukaemia (PLL) B cells. These mAb stain a minority of B- and T-cell leukaemias and approximately 20% of peripheral blood and tonsil T and B cells, activated with a variety of mitogens. Interestingly, all small cell lung cancer (SCLC) and bladder carcinoma lines examined were also stained by both mAb. On sections of normal and malignant tissue 1D1 and 2A6 show strong but distinct reactivity with epithelium, and in the case of ID1 staining is also present on endothelial tissue. The addition of purified 1D1 and 2A6 to Epstein-Barr virus (EBV)-transformed B-lymphoblastoid cell lines (B-LCL) and SCLC lines caused a significant increase in the rate of proliferation of these cells. Capping experiments have suggested that these two mAb, despite showing significantly different staining profiles, probably recognize distinct epitopes of the same surface molecule. These studies confirm that a lymphoid-cell associated antigen(s) detected by mAbs 1D1 and 2A6 is expressed on a wide range of normal and malignant cells and related cell lines.
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PMID:Lymphoid cells, small cell lung cancer cells and epithelial cells share a membrane determinant which effects cell proliferation. 248 7

A small number of human myelomas have been established as long term cultured cell lines. We report the characteristics of two new cell lines, designated SK-MM-1 and SK-MM-2, derived from 73 attempts to culture myeloma specimens. Both cell lines were grown from myeloma patients with hypogammaglobulinemia, kappa light chain proteinuria, and plasma cell leukemia. SK-MM-1 and SK-MM-2 had a plasmacytoid morphology, grew in RPMI complete medium with doubling times of 32 and 60 hr, respectively, and did not express Epstein-Barr virus nuclear antigen. Both cell lines secreted kappa light chains (0.9 and 1.1 micrograms/10(6) cells/ml per 48 hr for SK-MM-1 and SK-MM-2, respectively) but no heavy chains. SK-MM-1 and SK-MM-2 expressed the pan-B cell marker B1 and the late B cell/plasma cell marker BL3. In addition, SK-MM-2 expressed late B cell/plasma cell markers OKT10 and PCA-1. Neither cell line expressed T lymphocyte, myeloid, or early B lymphocyte markers. The presence of distinctive kappa and heavy chain gene rearrangements supported the clonal origin of both cell lines from kappa light chain-producing B cells. The two cell lines were markedly aneuploid and both carried a 14q+ marker chromosome. Human myeloma cell lines lacking heavy chain secretion may be useful to elucidate mechanisms of immunoglobulin gene regulation and to construct human-human hybridomas.
Leukemia 1989 Oct
PMID:Establishment and characterization of two human myeloma cell lines secreting kappa light chains. 250 99


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