Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0023473 (chronic myeloid leukemia)
 18,916 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Lymphocyte-dependent antibodies (LDA's) directed against antigenic determinants present on lymphoblastoid cell lines as well as human leukemia blast cells were demonstrated in heterologous antisera obtained by immunizing rabbits with a membrane fraction from RPMI-4265 (a lymphoblastoid cell line derived from a patient with chronic myelogenous leukemia). LDA was present at high titers against B-lymphoblastoid, myelomonocytic, and stem cell lines. The T-lymphoblastoid cell line MOLT-4, however, did not react. LDA was demonstrated against acute myelogenous as well as lymphoblastic leukemia cells. The reactivity was not directed against phytohemagglutinin-induced blastoid antigens, fetal antigens, or fetal calf serum. Absorptions with lymphoblastoid cell lines removed all LDA reactivity. Similar results were obtained by absorbing the rabbit antiserum with acute lymphoblastic and/or acute myelogeneous leukemia cells. These findings indicate the presence of cross-reactive antigens between lymphoblastoid cell lines and leukemia cells. Furthermore, cross-reactivity between acute lymphoblastic and acute myelogenous leukemia cells was demonstrated.
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PMID:Antigens shared by leukemic blast cell and lymphoblastoid cell lines detected by lymphocyte-dependent antibody. 105 51

The present experiment was undertaken to study what types of human cancers are responsive to the antiproliferative effects of suramin. The human malignant cells used were as follows: cervical cancer (HeLa), mammary cancer (MCF-7), bladder cancer (EJ), hepatoma (HuH-7, PLC/PRF/5), embryonal carcinoma (PA-1), in vitro transformed fibroblasts (KMST-6, SUSM-1, VA-13), five myeloma cell lines (KMM-1, KMS-5, KMS-11, KMS-12, RPMI 8226), Burkitt's lymphoma (Raji), acute promyelocytic leukemia (HL-60), chronic myelocytic leukemia (K562), Epstein-Barr virus nuclear antigen positive lymphoblastoid cells (KMS-9). The cells were treated with 25 to 100 micrograms/ml suramin for 72h. Proliferation of HuH-7 and two human myeloma cells (KMS-11 and KMS-12) was remarkably inhibited, and that of PA-1, PLC/PRF/5, KMST-6, two other myeloma cell lines (KMM-1 and KMS-5), Raji and HL-60, was moderately inhibited. In order to confirm part of the results obtained from in vitro experiments, in vivo experiments were also undertaken. The growth of HuH-7 cells transplanted subcutaneously into nude mice was significantly suppressed by intravenous injection of suramin. We discussed the possibility that certain types of human cancers, the growth of which seemed to be more or less dependent on polypeptide growth factors, might be sensitive to the antiproliferative effects of suramin.
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PMID:Antiproliferative effects of suramin on human cancer cells in vitro and in vivo. 148 40

A new human myeloid cell line has been established recently from the bone marrow cells of a patient with chronic myelogenous leukemia in blast crisis. The active proliferation and survival of the cells in RPMI 1640 medium containing fetal calf serum are clearly dependent on the presence of either natural or recombinant human granulocyte-macrophage colony-stimulating factor (rhGM-CSF). Despite permanent culturing in rhGM-CSF (100 U/mL), the cells do not differentiate and bear the myelomonocytic surface markers CD34, CD13, CD36, as well as HLA-DR, but not CD3, CD7, CD10, CD11b, CD14, CD20, or CD42b. The predominant karyotype, apart from tetraploidy in several cells, is 45, XX, -9, -17, -19, -22, 7p-, 9q+ (der t[9;22]), der (13q), with three additional marker chromosomes, from which one was observed in the patient's leukemic cells. On BglII-digested DNA, Southern blot analysis with bcr 5' as the probe detected two additional hybridizing restriction fragments of 8.6 and 11.0 kilobase pairs.
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PMID:Establishment and characterization of a granulocyte-macrophage colony-stimulating factor-dependent human myeloid cell line. 219 61

A megakaryoblastic cell line, termed T-33, was established from the peripheral blood of a patient with Philadelphia chromosome-positive chronic myelogenous leukemia in megakaryoblastic crisis. T-33 cells have been maintained in RPMI 1640 medium containing 10% fetal calf serum in a single cell suspension with a doubling time of 24-36 h for over 2 years. Giemsa-banded karyotypes were female hyperdiploid with a modal chromosomal number of 51, all cells including Philadelphia chromosome. The cells showed strong positivity for periodic acid-Schiff and alpha-naphthyl acetate esterase, and weak for alpha-naphthyl butyrate esterase, but were negative for myeloperoxidase. Flow cytometric analysis of cell surface markers showed the existence of HLA-DR, MY-7, MY-9, and a platelet antigen (Yukb), and no markers for T- or B-lymphocytes. Most of the cells fixed with acetone were positive for Factor VIII, platelet glycoprotein IIb-IIIa, IIIa (Yukb), and Ib, but negative for glycophorin A and hemoglobin. Ultrastructural platelet peroxidase was demonstrated in 2-3% of cells and the percentage of positive cells increased up to 20% after the treatment with 12-O-tetradecanoylphorbol-13-acetate. The cells contained small dense granules negative for platelet peroxidase, their number increasing threefold after 12-O-tetradecanoylphorbol-13-acetate treatment. Such treated cells frequently showed a complex of the demarcation membrane in the cytoplasm. T-33 responded thrombin to exhibit calcium influx. This cell line may be useful for the study of the early stage of megakaryocytic differentiation in human megakaryopoiesis.
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PMID:Establishment of a human megakaryoblastic cell line (T-33) from chronic myelogenous leukemia in megakaryoblastic crisis. 316 60

Conditioned media from the human myeloid leukemic cell line ML-2 contain a factor that inhibits the entry of normal CFU-GM into S phase of mitotic cycle as measured by the 3H-TdR suicide technique. This factor was detected in conditioned media prepared by incubating 5 X 10(6) ML-2 cells/ml or 1 X 10(6) ML-2 cells/ml in serum-free RPMI for 5 or 24 hours respectively, and was isolated by ultrafiltration through an XM 300 Diaflo membrane followed by chromatography on Sepharose 6 B. Ferritin, prepared from human placenta, had the same inhibitory effect on CFU-GM. Antibodies against human placental ferritin completely inactivated the inhibitory effect of both human placental ferritin and the factor released from ML-2 cells. The inhibitory activity produced by the cell-line ML-2 was considered as LIA (leukemia cell-derived inhibitory activity) earlier found in HL-60 cell line and AML and CML cells.
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PMID:Identification of leukemia cell-derived inhibitory activity (LIA) in conditioned media from human myeloid leukemic cell line ML-2. 348 46

T lymphocytes were derived by E rosetting from the peripheral blood (PB) and bone marrow (BM) of 15 patients with chronic granulocytic leukemia (CGL) in the chronic phase of their disease. T cells were also obtained from 12 healthy individuals. T cells were incubated overnight either in culture medium (RPMI) or RPMI plus pokeweed mitogen (PWM). The supernatants were then recovered and the cells washed in fresh RPMI. T cells from normal donors and from CGL patients were then cocultured with normal allogeneic marrow cells grown in soft agar for CFU-C colony formation. Target marrow cells were also grown in agar in the presence of T-derived supernatants. The results of this study can be summarized as follows. (1) Normal PB and BM T cells efficiently suppressed autologous and allogeneic CFU-C growth after PWM stimulation. (2) T cells derived from peripheral blood or marrow of CGL patients failed to inhibit CFU-C growth, whether pretreated with PWM or not. (3) The supernatants of PWM-treated normal T cells strongly inhibited CFU-C colony formation, whereas the supernatants of PWM-treated CGL T cells had no CFU-C/suppressor activity. These data indicate that T cells from CGL patients cannot be primed to become CFU-C suppressor cells after PWM: stimulation in vitro and cannot release a soluble inhibitor of granulopoiesis produced by PWM-primed normal T cells.
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PMID:Generation of CFU-C suppressor T cells in vitro. III. Failure of mitogen-primed T cells from patients with chronic granulocytic leukemia to inhibit the growth of normal CFU-C. 621 63

Monoclonal antibody T305, prepared by immunizing mice with the T-ALL derived cell line RPMI-8402, immunoprecipitates a single chain glycoprotein with m.w. 160,000 daltons (under reducing conditions) or 180,000 daltons (under nonreducing conditions). In immunofluorescence assays, antibody T305 reacted with a subpopulation of T cells in normal blood (22 +/- 6%), thymus (28 +/- 11%), and lymph node (24 +/- 6%). Increased frequency of T cells reactive with antibody T305 was found in peripheral blood of patients with infectious mononucleosis (greater than 80%), graft-vs-host disease after bone marrow transplantation (65 +/- 11%), acquired immunodeficiency syndrome (53 +/- 12%). The T cells in synovial fluid of patients with rheumatoid arthritis had increased frequency of antibody T305 reactive cells (59 +/- 8%) as compared to their peripheral blood (18 +/- 7%). Two color immunofluorescent studies demonstrated that the T305+ T cells predominantly co-stained with antibody Leu 2a (suppressor/cytotoxic subset) in both normals and disease state blood. After cell sorting to obtain T305+ and T305- subpopulations, we demonstrated that a) natural killer and antibody-dependent cellular cytotoxicity activity in normal blood was in the T305+ but not T305- T cells; b) cytotoxic T cells induced by mixed lymphocyte reaction were predominantly T305+; c) T305- T cells could be induced in vitro to express T305 antigen by mitogens or allogeneic B cells; d) the DNA content of T305+ and T305- T cells in normal blood was similar (greater 95% of cells with G0/G1 level); e) after mitogen stimulation, T305 antigen induction on previously T305- cells occurs before S-phase; and f) significantly more [3H]-thymidine after mitogen stimulation was incorporated by originally T305- cells than by originally T305+ cells (p less than 0.001). The T305 antigen was not restricted to T cells because it was also found on myeloid precursors in bone marrow but was not present on polymorphonuclear leukocytes, red blood cells, platelets, muscle, liver, skin, kidney, lung, or brain. Antibody T305 was found on 24/25 cases of acute leukemia (6 T-ALL, 10/11 cALL, 7 AML, and 1 AMOL) but not on 18 cases of chronic leukemia (B-CLL, T-CLL, null CLL, CML). The importance of the T305 antigen is that it is present on a high number of T cells in certain autoimmune diseases and on virtually all acute leukemia cells. Its distribution on immature and in vitro activated cells suggests that it may represent a receptor for signals related to cellular replication or differentiation.
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PMID:A novel cell surface antigen (T305) found in increased frequency on acute leukemia cells and in autoimmune disease states. 660 45

In this study we compared rates of apoptosis, survival and metabolic activity from CML peripheral blood neutrophils with peripheral blood and bone marrow neutrophils from healthy volunteer donors and studied the influence of the disease stage and of cytokines including G-CSF, GM-CSF and IL-1beta on these parameters. Quantification of apoptosis by morphology, diphenylamine DNA fragmentation assay and by gel electrophoresis showed similar rates of apoptosis in chronic phase CML and normal peripheral blood neutrophils when the cells were incubated in RPMI + FCS or in serum-free medium. However, there were lower rates of apoptosis in accelerated and blast phase CML neutrophils (p < .001) and in normal bone marrow neutrophils (p < .001) compared to normal peripheral blood neutrophils (incubated in RPMI + FCS). Survival among neutrophils from chronic phase or accelerated/blast phase CML patients was significantly longer (p < 0.002 and p < 0.001, respectively) than among normal peripheral blood neutrophils but neutrophils purified from normal bone marrow had a survival rate which fell between that of normal peripheral blood and chronic phase CML patients. When the cells were incubated in RPMI + autologous sera, neutrophils from chronic phase CML patients showed markedly lower rates of apoptosis (p < 0.001) and maintained higher metabolic activities (p < 0.002) compared to normal neutrophils. G-CSF and GM-CSF were found to considerably decrease the rate of apoptosis in chronic phase CML neutrophils (p < 0.001 and p = 0.008 respectively) while IL-1beta did not show any antiapoptotic effect. It is suggested that the endogenous production of growth factors may therefore participate in delaying apoptotic cell death, during the progression of CML.
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PMID:Apoptosis in chronic myelogenous leukemia: studies of stage-specific differences. 913 Jun 20

Naive T lymphocytes specific for a given primary antigen occur in low frequencies and require the relevant antigen to be presented by specialist antigen presenting cells (APC), i.e., dendritic cells (DC). For these reasons, the in vitro induction of primary T lymphocyte responses remains a significant technical challenge. We have attempted to improve current strategies for generating in vitro responses by optimising (i) isolation and concomitant activation of DC from peripheral blood, (ii) uptake, processing and presentation of antigen by DC and (iii) antigen driven T lymphocyte proliferation. We established that RPMI 1640 media supplemented with 10% autologous serum resulted in the best yield of CMRF-44+, CD14-, CD19- DC after enrichment over a Nycodenz gradient. Optimal presentation of whole protein and peptide antigen was achieved by addition after the purification of the APC, i.e., at the start of the T lymphocyte proliferation assay. RPMI 1640 supplemented with 10% autologous serum or plasma supported the best antigen driven specific T lymphocyte responses. Using these optimised conditions, we compared the efficacy of PBMC and purified blood DC for priming T lymphocyte responses to the chronic myeloid leukaemia (CML) specific bcr-abl (b3a2) peptide. Peptide specific T lymphocyte responses were generated with both purified DC and whole PBMC, suggesting that T lymphocyte precursor frequency was the limiting factor in these experiments. These results will aid in the generation of human T lymphocyte lines to primary antigens, for in vitro and therapeutic applications.
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PMID:Optimisation of the conditions for generating human DC initiated antigen specific T lymphocyte lines in vitro. 983 89

The goal of this work was to optimize dendritic cell (DC) preparations obtained from patients suffering from chronic myeloid leukemia (CML) and compare them with DC prepared from normal CD14+ mononuclear cells (MNC). We studied normal DC and bcr-abl+ leukemic DC (CML-DC) yields, expression of membrane molecules, differentiation status, and ability to stimulate T cells. We isolated DC precursors from PBMC by CD14-specific immunoadsorption and cultured them for 7 days in GM-CSF and IL-4, followed by a 3-day incubation to fully differentiate the cells. We evaluated cultures of CML-DC using RPMI 1640 medium supplemented with FBS and X-VIVO 15 medium containing human AB serum. In contrast to cells matured in RPMI 1640, virtually all cells incubated in X-VIVO 15 expressed CD83, a marker of mature DC. CML-DC and normal DC were indistinguishable in expression of CD83, resulting in the highest percentage reported so far. The yields of normal DC and CML-DC from CD14+ cells were indistinguishable. The percentage of bcr-abl+ cells in PBMC varied among patients between 65% and 97% and the final CML-DC preparations were >98% bcr-abl+ the highest purity of bcr-abl+ cells to date. Normal DC and CML-DC were equally effective in stimulating proliferation of allogeneic and autologous T cells. These techniques provide highly enriched, mature, functional CML-DC.
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PMID:Optimizing preparation of normal dendritic cells and bcr-abl+ mature dendritic cells derived from immunomagnetically purified CD14+ cells. 1073 77


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