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

Human NK activity is radiosensitive under the control of X-linked genes. We have evaluated the expression of these genes in other forms of cellular cytotoxicity. The NK radioresistant and radiosensitive phenotype is expressed in ADCC. Specific cellular cytotoxicity, generated in a MLC with a radiosensitive donor as responder, was radioresistant. NK-like activity recruited from nonadherent cells of radiosensitive subjects stimulated with allogenic cells, mitogens (PHA, Con A or PWM), or recall antigens (TT or PPD) was radioresistant. The acquisition of radioresistance was relatively rapid, beginning within 24 hr after exposure to PHA, prior to detectable proliferation. Radioresistance of MLR augmented NK-like activity was maximal 3 days after initiation of the culture. MLR augmented NK-like activity was spared by the immunosuppressive polypeptide antibiotic CsA at doses up to 1 micrometer/ml. CsA did, however, reduce acquisition of radioresistance by the NK-like activity at doses above 0.01 mu gm/ml, a concentration which does not inhibit uptake of 3H-thymidine but does reduce the level of specific CML. These data suggest that mitogens and antigens, including allogeneic cells, are recruiting radioresistant NK-like activity which can be distinguished from the radiosensitive spontaneous NK activity of the cell donor. Further, in the MLR, both radiosensitive and radioresistant NK-like activity may be recruited.
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PMID:Radioresistance of culture-induced augmented natural killer-like activity. 619 19

In the present paper attempts have been made to investigate suppressor cell activity in CML patients in first and subsequent remissions in order to study the relationship between suppressor cell activity and progression of the disease. For this purpose, the ability of Con A activated suppressor cells from peripheral blood of CML patients in 1st, 2nd and 3rd remission to suppress PHA response of autologous lymphocytes is investigated and compared with that of normal healthy donors. The ability of Con A activated cell population to form rosettes with autologous RBCs (ARFC) is also investigated. The results indicate that lymphocytes from CML patients in 1st (61.8 +/- 6.1%), 2nd (62.6 +/- 3.0%) and 3rd (55.3 +/- 4.8%) remissions show significantly high suppressor cell activity than normal healthy donors (36.5 +/- 1.9%) when activated with Con A. Similarly, generation of spontaneous suppressor cell activity was also higher in 1st (23.3 +/- 4.7%) and 2nd (25.3 +/- 4.2%) remission lymphocytes than controls (10.1 +/- 2.5%). In the 3rd remission however, the spontaneous suppressor cell activity (14.5 +/- 3.2%) was comparable to controls. Thus it appears that a higher suppressor cell precursor population is present in CML patients in remission. However, this could not be correlated with the progression of the disease. CML patients in 1st remission also revealed an increased percentage of ARFC which correlated with the suppressor cell function. The ARFC activity tested in a few patients in subsequent remissions was comparable with controls although functional suppressor activity was increased.
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PMID:Concanavalin A induced suppressor cell activity and autorosette forming cells in chronic myeloid leukemia patients. 622 43

Tumor cells obtained from leukemia and lymphoma patients were investigated for specific insulin receptors. Using radioactive 125I-labeled insulin, specific insulin binding sites were demonstrated on most acute lymphocytic leukemia (ALL) and acute myelocytic leukemia (AML) cells, including acute promyelocytic leukemia (APL), chronic myelocytic leukemia (CML), and acute monocytic leukemia (AMoL) cells. Insulin receptors were not found on chronic lymphocytic leukemia (CLL) and malignant lymphoma (ML) cells. Specific insulin binding sites were also found on monocytes and thymocytes after treatment with phytohemagglutinin (PHA-P), but not on inactivated tonsil cells, peripheral blood lymphocytes, or thymocytes. There was no inverse correlation between the content of insulin receptors and the basal level of circulating insulin. These data suggest that the insulin receptor may be a new marker of acute leukemia and chronic myelocytic leukemia.
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PMID:Insulin receptors on leukemia and lymphoma cells. 634 73

The cell membrane fraction from c-ALL, B-ALL, Ph' + ALL, B-CLL, T-CLL, AML, blastic-CML, normal leukocytes, PHA-stimulated lymphocytes and several T, B and myeloid human leukemic cell lines has been used in different cell types to demonstrate different patterns of glycosyltransferase activity. Both B- and T-CLL cell membranes have low fucosyltransferase B and A activity compared to acute leukemias; while sialyltransferase activity is higher in B- than in T-CLL. AML cell membranes and ML-1 human myeloblast cell line membranes have exceptionally high fucosyltransferase A activity compared to all other leukemic cells or cell lines. Human leukemic B cell lines expressed cell membrane sialyltransferase, fucosyltransferase B and probably fucosyltransferase A activity several times higher than T cell lines. Human myeloid cell lines ML-1 and HL-60 express 5- to 20-fold higher galactosyltransferase activity than human leukemic T and B cell lines. Both sialyltransferase and galactosyltransferase activity were higher in all leukemic cells than in normal leukocytes and PHA-stimulated normal lymphocytes. This is the first study carried out on glycosyltransferases using cells obtained from leukemic patients characterized immunologically. These results indicate that all glycosyltransferase activity, with the exception of fucosyltransferase activity in CLL, were higher in leukemic cells than in normal cells. Moreover, large differences in these enzymes, e.g. very high galactosyltransferase activity in myeloid cell lines compared to B and T cell lines, of fucosyltransferase A in AML and myeloblast cell lines compared to all other cells, and of sialyltransferase in B-CLL or B cell lines compared to T-CLL or T cell lines, could be useful in characterizing certain leukemias and hematopoietic cell lines.
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PMID:Glycosyltransferase activities in leukemic cells from patients and human leukemic cell lines. 641 47

The suppressive effects of four agents on several types of in vitro immune response and on in vitro responses to T and B mitogens were studied comparatively in spleen cells from C57B1/6 mice, previously injected with each of these agents. It was found that the in vitro PFC response to sheep erythrocytes was the most constantly and extensively inhibited: from 56% after treatment with Con A to 85% after treatment with HSA; LPS and C. parvum also provoked a strong inhibition (74-78%). Inhibition of MLC was constant but less effective, ranging from 36% (LPS) to 57% (C. parvum); HSA and Con A depressed it by about 50%. The CML reaction was substantially inhibited by C. parvum (50%), moderately by Con A and LPS (respectively, 23 and 28%) and slightly by HSA (15%). The inhibition of mitogenic response to PHA and LPS varied widely with the agent used: the PHA response was strongly inhibited by Con A (84%) to a lesser extent by C. parvum (54%) and even less by LPS (27%), whereas HSA did not affect it. LPS reactivity was well inhibited by C. parvum (57%), moderately by Con A (25%), slightly by HSA and not at all by LPS. Most of these agents produced a slight but significant prolongation of skin graft survival time. In vitro experiments using mixtures of spleen cells from treated and normal animals showed that these inhibitory effects were mediated by suppressive cells that developed as a result of the treatment used. The degree of inhibition observed in the mixed cultures satisfactorily paralleled the direct inhibition observed in cells from treated animals. The more consistently suppressive agents seemed to be C. parvum and Con A, the effects of the other two (HSA and LPS) on the cellular responses studied were less regular.
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PMID:Non-specific inhibitory processes of immunological and mitogenic cellular responses. 644 6

Lymphocytes from 13 chronic myeloid leukaemia (CML) patients in remission were tested for their ability to differentiate in vitro into a cell population cytotoxic to autochthonous target leukaemic cells. CML remission lymphocytes were cultured in vitro with autochthonous leukaemic cells and allogeneic normal lymphocytes from an unrelated donor, singly or in combination. The cytotoxic lymphocytes obtained after 7 days of culture were tested for their ability to kill autochthonous leukaemic cells in a 3h 51Cr-release assay. It was found that with the allogeneic stimulus alone, cytotoxicity was generated in 5/13 cases, whilst stimulation of lymphocytes with autochthonous leukaemic cells alone induced cytotoxicity in 7/13 cases. In contrast, anti-leukaemic cytotoxicity was shown in 12/13 cases when responder lymphocytes were stimulated with both autochthonous leukaemic and unrelated allogeneic normal lymphocytes. The specificity of cytotoxicity was confirmed using other targets such as autochthonous PHA-transformed lymphoblasts and mouse L1210 cells. In 1/5 cases, CML remission lymphocytes stimulated with autochthonous leukaemic cells showed cytotoxicity to PHA-transformed autochthonous normal lymphoblasts, whilst 1/4 patients showed nonspecific cytotoxicity to L1210 cells when lymphocytes were cultured in MLC or MLTC, as well as in a 3-cell assay.
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PMID:In vitro generation of lymphocytotoxicity to autochthonous leukaemic cells in chronic myeloid leukaemia. 645 Jun 3

T-cells were investigated by the E rosette assay, PHA stimulation, allogeneic MLC and CML responses, in a group of 100 healthy aged people over 70 years old, and compared to young control individuals less than 45 years old. No major difference was found between the two groups, except for PHA stimulation which was significantly reduced in old individuals when low mitogen concentration was used. These observations suggest that only some T cells subsets are affected by ageing, without modification of the total T lymphocyte number. Contrarily, the phagocytic activities of polymorphonuclear cells assessed in a group of 38 aged people were dramatically decreased, using either the NBT test or a direct phagocytosis assay.
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PMID:Immunological studies in human ageing. I. In vitro functions of T cells and polymorphs. 645 27

Some CTLs recognize HLA-structures in a different way than antibodies, i.e. they may identify other epitopes than antibodies or may define genetically distinct structures. From population studies, in vitro educated CTLs were selected giving rise to significant lysis on PHA-lymphoblasts in the absence of the sharing of HLA-A, B, (C) determinants between stimulator and target lymphocytes. Based on pair-wise correlations these CTLs form 3 clusters, identifying structures associated to HLA-markers. Subsequent testing in 14 complete families of greater than or equal to 4 children allowed the observations: (1) CML-traits assigned on the basis of single CTLs often segregated in a non-mendelian way or independent of HLA. (2) Assignment made on the basis of CTL-clusters segregated with HLA. (3) in 2 informative HLA-B/D, DR recombinant families, CML-traits segregated with HLA-B. (4) No haplotype could be assigned more than one CML-trait.
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PMID:Typing by cytotoxic lymphocytes. Genetics of HLA-non-A, B, C determinants - family studies. 646 Oct 89

Human hemopoietic pluripotent progenitors form multilineage colonies when cultured in methylcellulose with medium conditioned by leukocytes in the presence of phytohemagglutinin (PHA-LCM) and erythropoietin (EPO). We have examined their frequency, culture requirements and proliferative activity in 20 peripheral blood and 29 bone marrow specimens from patients with CML in chronic phase. Multilineage colonies developed under regular culture conditions in approximately 50% of all samples. The frequency ranged from 1-36 per 2 X 10(5) mononuclear cells of density less than 1.077 gm/ml. The requirements for PHA-LCM and EPO varied for patients with CML when compared to normal individuals; i.e., cells from some patients gave rise to mixed colonies with substantial erythroid components in the absence of PHA-LCM or without addition of the usually required EPO concentrations. The proliferative activity of CFU-GEMM was assessed using a short-term exposure to tritiated thymidine (3HTdR) prior to plating. The plating efficiency in all bone marrow and peripheral blood samples was reduced to 40-70% of the unexposed controls. In contrast, the plating efficiency after exposure to 3HTdR in normal individuals usually ranged from 70-90% of controls for bone marrow samples and from 85-100% of controls for peripheral blood samples. Thus, an increased proliferative rate of pluripotent hemopoietic progenitors is a consistent feature of CML patients. In addition, at least in some patients, different requirements for erythropoietin or PHA-LCM were observed when compared to normal culture conditions.
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PMID:Pluripotent hemopoietic progenitors (CFU-GEMM) in chronic myelogenous leukemia. 658 83

The nucleolus organizer activity of bone marrow cell chromosomes has been studied by silver staining (Howell, Black, 1980) for 6 healthy donors, 24 patients with acute leukemia, and 17 patients with chronic myelocytic leukemia, including 6 cases of blast crisis. In respect to the nucleolus organizer silver staining pattern, bone marrow cells of donors and of patients with leukemias appeared to be more heterogeneous than PHA-stimulated lymphocytes of the same individuals. The average numbers of Ag-stained nucleolus organizers per metaphase in donors (5.2 +/- 0.22), patients with chronic phases (4.9 +/- 0.30), and patients with blast crisis of myelocytic leukemia (5.3 +/- 0.37), and in those with acute leukemia (5.2 +/- 0.46) were lower than those in PHA-stimulated lymphocytes of the same individuals; a great part of bone marrow cell mitoses (from 19 up to 46%) being Ag-negative in all the above groups. A conclusion is made that the heterogeneity in silver staining of the nucleolus organizers in bone marrow cells is due mostly to differences in their mitotic cell maturity degrees. Prospects of employment of silver staining of nucleolus organizers in cells for clinical purposes are discussed.
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PMID:[Nucleolar organizer activity of normal and leukemic cells in human bone marrow]. 658 80


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