Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0023418 (leukemia)
 93,477 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The BCL2 (B cell lymphoma/leukemia-2) and C-HA-RAS oncogenes encode membrane-associated proteins of 26 and 21 kilodaltons, respectively. Although RAS proteins have long been known for their ability to bind and hydrolyze GTP, recent investigations suggest that BCL2 encodes a novel GTP-binding protein (S. Haldar, C. Beatty, Y. Tsujimoto, and C. M. Croce, Nature [London] 342:195-198, 1989). Cotransfection of BCL2 and HA-RAS oncogenes resulted in morphological transformation of early-passage rodent fibroblasts, rendering these cells tumorigenic in animals and enabling them to grow in semisolid medium. In contrast, cotransfection of BCL2 with oncogenes that encode nuclear proteins (E1A and C-MYC) did not produce malignant transformation, whereas HA-RAS did complement with these genes. These findings suggest that proteins encoded by oncogenes such as BCL2 and HA-RAS, although having similar subcellular locations and perhaps similar biochemical properties, can regulate distinct complementary pathways involved in cellular transformation.
 ...
PMID:Complementation by BCL2 and C-HA-RAS oncogenes in malignant transformation of rat embryo fibroblasts. 219 51

Antisense oligodeoxynucleotides specific for sequences in mRNAs from the B-cell lymphoma/leukemia-2 (BCL2) gene were used to inhibit the growth in culture of a human leukemia cell line, 697. Normal phosphodiester (PO) and nuclease-resistant phosphorothioate (PS) oligodeoxynucleotides were compared with regard to specificity, potency, and kinetics. Both PO and PS antisense BCL2 oligodeoxynucleotides were specific inhibitors of cellular proliferation, since sense versions of these synthetic DNAs were inactive at similar concentrations. Specificity was further confirmed by quantitative immunofluorescence studies, showing that PO and PS antisense BCL2 oligodeoxynucleotides (when used at appropriate concentrations) reduced levels of BCL2 protein without influencing expression of HLA-DR and other control antigens. The onset of inhibition by PO oligodeoxynucleotides was faster, with reductions in cell numbers occurring within 1 day of addition to cultures, in contrast to phosphorothioates, which were ineffective until 3-4 days. Phosphorothioates were more potent that phosphodiesters, however, with half-maximal inhibition of leukemic cell growth occurring at concentrations 5-10 times lower. As expected from previous studies demonstrating the importance of BCL2 for regulating lymphoid cell survival, BCL2 antisense oligodeoxynucleotides also led to 697 leukemic cell death through sequence-specific mechanisms, with reductions in cellular viability generally lagging the inhibitory effects on cellular growth by about 2 days. Taken together, these data indicate that PO and PS oligodeoxynucleotides targeted against the human BCL2 protooncogene can be sequence-specific inhibitors of leukemic cell growth and survival.
 ...
PMID:Antisense-mediated inhibition of BCL2 protooncogene expression and leukemic cell growth and survival: comparisons of phosphodiester and phosphorothioate oligodeoxynucleotides. 220 17

Antiidiotype (Id) antibodies identify unique determinants within the surface immunoglobulin (Ig) that are present on B-cell tumors. Anti-Ids have been used for diagnosis and therapy of B-cell lymphoma and leukemia. A panel of 29 anti-Id monoclonal antibodies (MoAbs) that recognize shared idiotypes (SIds) on B-cell lymphomas was tested for reactivity with both B-cell leukemias and lymphomas. Ten of 40 (25%) cases of chronic lymphocytic leukemia (CLL) reacted with at least one of the 29 anti-SId MoAbs. Three cases reacted with more than one anti-SId MoAb, but there was no repetitive pattern of a single anti-SId MoAb reacting with a large proportion of CLL cases. In contrast, for B-cell lymphoma, in which 11 of 31 (36%) cases reacted, one anti-SId (B4-1) reacted with five of the positive cases; all were diffuse histology. Restricted anti-SId reactivity may lead to important insights into the etiology of certain B-cell lymphomas. In addition, these anti-SIds may obviate the need to develop "tailor-made" antibodies for individual patients.
 ...
PMID:Shared idiotype expression by chronic lymphocytic leukemia and B-cell lymphoma. 222 30

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.
 ...
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

In a series of 139 spleens involved by non-Hodgkin's lymphoma, we found that each type of lymphoma (as classified according to the Kiel classification) has a specific pattern of infiltration in the red and white pulp. Tumor infiltration in preexistent follicles was not a feature of B-cell lymphomas, but tumor nodules were found in the red pulp nonfiltering areas in cases of immunocytoma (small lymphocytic plasmacytoid) and centroblastic-centrocytic lymphoma (follicle center-cell lymphoma). B-chronic lymphocytic leukemia and centrocytic-centroblastic lymphoma were located along central arteries of T-cell areas. T-cell areas were infiltrated by B-prolymphocytic leukemia, immunocytoma, centrocytic lymphoma (lymphocytic lymphoma of intermediate differentiation), and T-cell lymphoma/leukemia. The red pulp showed diffuse involvement in leukemic cases. Additionally, there was pericapillary growth in all cases of low-grade B-cell lymphoma. The findings, which are related to the physiological counterparts of the lymphoma cells, contribute to our knowledge of the routes of circulation as well as the homing areas of lymphocytes in the human spleen.
 ...
PMID:The distribution of non-Hodgkin's lymphoma in the lymphoid compartments of the human spleen. 250 66

We investigated the expression of fos oncogene proteins in lymphoproliferative disorders, using a monoclonal antibody (FO-120) that was prepared against a synthetic oligopeptide of fos protein (amino acid sequence from 127 to 152). Although peripheral blood leukocytes were rarely positive for FO-120, they were transiently stained after lectin (PHA) stimulation. After culture with IL-2 for 1 or 2 weeks, less than 40% of the lymphocytes weakly reacted with FO-120, whereas strongly positive cells were detected in more than 70% of cells in half the T-cell lines established from preleukemic state of adult T-cell leukemia (pre-ATL) and all of ATL derived T-cell lines. All in vivo specimens of non-Hodgkin's malignant lymphomas, except for one case of T-cell lymphoma were also strongly positive. In addition, the extent of the antibody reactivity correlated with the histopathological grade of malignancy in B-cell lymphoma. The reactivity to most AILD-IBL lesions overlapped with that to T-lymphomas, and could be distinguished from that to reactive lesions. FO-120 appears to be a useful tool for detecting early neoplastic changes in lymphoproliferative disorders.
 ...
PMID:Detection of fos oncogene products by monoclonal antibody FO-120 in lymphoproliferative disorders. 251 20

Mouse monoclonal antibodies were produced against MT-2 cell line derived from adult T-cell leukemia or human T-cell leukemia virus-rich fraction therefrom. Two IgG1 antibodies, Ta60a and Ta60b, were found to be reactive not only with cell lines derived from adult T-cell leukemia or cutaneous T-cell lymphomas, but also with activated peripheral blood lymphocytes, suggesting the similarity of Ta60 antigen group to Tac antigen which is present on interleukin 2 receptor. Thus, the relationship among these antigens was studied. Two Ta60 antibodies and Tac antibody immunoprecipitated the molecule with almost identical electrophoretic mobility, approximately a Mr 60,000 antigen from [3H]glucosamine-labeled activated peripheral blood lymphocytes or MT-2, MT-1, or ATN-1 cells from adult T-cell leukemia and a Mr 53,000 antigen from HUT-102 cells derived from cutaneous T-cell lymphomas. Further, Tac antibody was found to immunoprecipitate Ta60b molecule on 125I-labeled MT-2 cells by sequential immunoprecipitation, indicating that these two epitopes are on the same molecule. Antibody binding inhibition assays with either 3H-labeled Ta60a or Ta60b antibody demonstrated that Ta60a and Tac are the same epitope, but different from Ta60b. Thus, at least two epitopes were demonstrated to be present on interleukin 2 receptor molecule. However, Ta60b antibody showed almost no blocking effects on proliferation of an interleukin-2-dependent cell line, whereas Ta60a antibody did. Various hematopoietic tumor cells were typed with these two antibodies, but the results with Ta60b antibody were described, because they showed a similar specificity. Ta60b antibody reacted with all adult T-cell leukemia cases, but did not react with T-cell acute lymphoblastic leukemia, lymphoblastic lymphoma, or mature T-cell lymphoma. Interestingly, 3 of 12 acute myeloblastic leukemia and 2 of 5 chronic myelocytic leukemia in blastic crisis showed positive reactions. One-third of B-cell chronic lymphocytic leukemia and B-cell lymphoma as well as a few B-cell lines were also weakly reactive with this antibody. A part of the results with direct tests was confirmed by the absorption tests. The results obtained demonstrated the presence of Ta60b on a certain fraction of malignant hematopoietic cells of other than T-cell origin.
 ...
PMID:Two mouse monoclonal antibodies detecting two different epitopes of an activated lymphocyte antigen on adult T-cell leukemia cells. 257 77

A new B-lymphoma cell line (DEAU-cell line) was established from a diffuse large-cell lymphoma (centroblastic type) and was successfully grafted in athymic nude mice. Monoclonal antibodies (MoAbs) were generated using splenocytes of DEAU-tumor bearing mice. Before the fusion experiments, cellular immunity of the mice bearing growing DEAU tumors was restored by injection of spleen cells from conventional Balb/C mice. Spleen cells from conventional Balb/C mice immunized with DEAU-cell line were also used for the generation of MoAbs. Four MoAbs (DBB.42 and DBA.44 from normal Balb/C mice, and DNA.7 and DND.53 from athymic nude mice) were investigated because they identified B-cell-associated antigens not destroyed by fixatives. DBB.42 recognized a pan-B cell-associated antigen (molecular weight (mol wt) = 45 Kd). DBA.44 detected a B-cell antigen (mol wt not determined) expressed on a subpopulation of B lymphocytes in the mantle zone of lymphoid follicles. DNA.7 also defined a B-cell antigen (43 Kd) mainly expressed on germinal center cells. Similarly, DND.53 recognized a B-cell antigen (two bands of mol wt 20 Kd and 35 Kd, respectively) mainly expressed on germinal center cells and mantle zone lymphocytes and interdigitating reticulum cells in the paracortical area. Major differences were found in the reactivities of these MoAbs on malignant lymphomas. DBB.42 was positive with almost all B-cell lymphomas and some T-cell lymphomas. Within the group of low-grade B-cell lymphomas, DBA.44 reacted principally with hairy-cell leukemia. DNA.7 reacted mainly with high-grade B-cell lymphomas with a weak positivity in low-grade B-cell lymphomas. DND.53 reacted with all but one B-cell lymphoma, cells of histiocytosis X, and Reed-Sternberg cells. These findings indicate that new MoAbs can be generated by using spleen cells from athymic mice bearing human tumors as well as by new lymphoid cell lines. The MoAbs so generated, as in the present study, are deemed potentially useful for the recognition of B-cell lymphomas in routine diagnostic histopathology. In addition, DND.53 could be of value for the diagnosis of histiocytosis X and the detection of Reed-Sternberg cells in Hodgkin's disease.
 ...
PMID:Production of anti-B monoclonal antibodies (DBB.42, DBA.44, DNA.7, and DND.53) reactive on paraffin-embedded tissues with a new B-lymphoma cell line grafted into athymic nude mice. 267 17

The bcl-2 (B cell lymphoma/leukemia-2) gene at band 18q21 is involved in t(14;18) chromosomal translocations in most follicular lymphomas and occasional other human B cell malignancies, where it becomes juxtaposed to the transcriptionally active immunoglobulin (Ig) locus at 14q32. Regulation of bcl-2 gene expression was investigated in neoplastic lymphoid cell lines containing normal #18 chromosomes or a t(14;18) translocation with regard to steady-state mRNA levels, RNA stability, transcription rates, and DNA methylation. High steady-state levels of bcl-2 mRNA, and proportionally high rates of bcl-2 transcription (measured in isolated nuclei), were found in B cell lines containing t(14;18) translocations. The half-life of bcl-2 mRNA (approximately 2-3 hr) was similar in all cell lines examined, including a t(14;18)-containing follicular lymphoma cell line, which has a translocated and rearranged bcl-2 gene that produces bcl-2/Ig fusion transcripts. However, in the presence of cycloheximide (inhibitor of protein synthesis), the half-life of some of the bcl-2/Ig mRNAs produced by these cells was prolonged, indicating that in some circumstances mRNA stability may contribute to deregulated bcl-2 expression. Despite stabilizing some bcl-2 mRNAs, the overall effect of treating cell lines with cycloheximide was a reduction in the levels of accumulated bcl-2 mRNAs through inhibition of bcl-2 gene transcription. These latter data provide indirect evidence that short-lived transacting factor(s) regulate transcription of the human bcl-2 gene in lymphoid cells with or without a t(14;18) translocation. No clear correlation was discovered between bcl-2 gene methylation and transcription.
 ...
PMID:Regulation of bcl-2 gene expression in lymphoid cell lines containing normal #18 or t(14;18) chromosomes. 277 9

The BCL2 (B cell lymphoma/leukemia -2) and C-MYC oncogenes become activated by chromosomal translocations involving the immunoglobulin heavy chain locus in human follicular lymphomas and Burkitt lymphomas, respectively. Though much is known about the biological actions of C-MYC, little information is available concerning the functions of BCL2, particularly in human B cells. Using a gene transfer approach we contrasted the effects of deregulated BCL2 and C-MYC expression in a human EBV-immortalized B cell line GM607B. Both BCL2 and C-MYC enhanced the ability of GM607B cells to grow in reduced serum and in limiting dilution cultures. These findings provide direct evidence that BCL2 can alter the growth characteristics of human B lymphocytes, thus strengthening arguments for its role in the pathogenesis of human lymphomas.
 ...
PMID:Deregulated BCL2 expression enhances growth of a human B cell line. 278 59


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>