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Query: UMLS:C0023418 (leukemia)
 93,477 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The mechanisms of paraneoplastic hypercalcemic syndromes are heterogeneous. Neoplastic hypercalcemia without bone metastatic disease is caused by parathyroid hormone related protein, whose action is comparable to parathyroid hormone. Growth transforming factors, platelet derived growth factor, tumor necrosis factors and interleukin 1 are also involved in humoral hypercalcemia of malignancy. In addition to these substances, hypercalcemia in bone metastatic disease may be related to PGE. Tumor necrosis factors and interleukin 1 play a major role in multiple myeloma as well as in Adult T cell Leukemia/Lymphoma where overproduction of vit D3 by lymphomatous cells can also be significant.
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PMID:[Hypercalcemia and neoplasms: recent advances in pathogenesis]. 229 Oct 7

Our recent establishment of several permanent in-vitro cell lines from Brown Norway rat leukemia (BNML) and the development of a clonogenic assay prompted us to undertake detailed studies on the growth control mechanism of a cell type which for several years has served as an animal model for human AML and preclinical studies. So far, these cells have no defined biological regulators but require intricate cellular interactions to sustain their growth. The effects on cell growth and clonogenicity, of agents known to modify the intracellular levels of cyclic nucleotides, were analysed. Here we report that CT binding strongly inhibited cell growth at a wide range of concentrations (10(-6)-10(-14) M) while beta chain pentameric subunits or alpha chain had no effects. Cell growth was inhibited in a dose-dependent manner. The ligand-receptor interactions mediated the alpha chain's transit through the membrane; the adenylate cyclase activation and the rise in c-AMP levels (60 min) resulted in DNA synthesis arrest (5 h), then finally ended in cell death (24-48 h). A significant decrease in the clonal ability of treated cultures was seen. A decrease of up to five logs in the clonogenic cell number was observed after 48 h of toxin treatment (10(-7) M). The growth inhibition of CT were reproduced by several agents (PGE, theophylline, isobutylmethylxanthine) known to raise intracellular c-AMP levels. Data are commented from a biochemical approach to intracellular events controlling the cell growth of this leukemia. The potential interests of c-AMP inducing agents on the eradication of this leukemia by ex-vivo marrow treatments are also considered.
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PMID:On growth regulation of the rat promyelocytic leukemia (BNML): growth inhibition and eradication of clonogenic cells by cholera toxin. 243 59

The rat promyelocytic leukemia cell line BNML is highly sensitive to cAMP elevating agents, and to cholera toxin (CT) in particular: 99.9% of the cells are killed in less than 48 hr of toxin treatment. We described here a subclone of the same leukemia, which, in contrast, is completely resistant to CT but still sensitive to other cAMP inducers. This locates the defect responsible for CT resistance at the membrane, somewhere between surface CT receptors and adenylate cyclase. CT-resistant BNML cells (CTR-BNML) do have surface CT receptors (several thousands per cell). Adenylate cyclase activity in CTR-BNML cells is not stimulated by cholera toxin. Other GS mediated stimulation of adenylate cyclase (by PGE, isoproterenol, histamine, NaF) remains relatively high, though 25-60% lower than in CTS-BNML cells. These results suggest that a specific adenylate cyclase defect is involved in the resistance of CTR-BNML cells to cholera toxin.
Leukemia 1989 Apr
PMID:Cholera toxin resistance associated with deficient adenylate-cyclase activity in a subclone of the rat promyelocytic leukemia (BNML). 253 85

Essential fatty acids, from which PG derive, can participate in development and regulation of immune responses and have been shown to suppress inflammation and tissue injury in animal models. In this report, we investigate the effects of the immediate (DGLA, precursor to PGE1), arachidonic acid (AA, PGE precursors, dihomogamma linolenic acid (DGLA, precursor to PGE1), arachidonic acid (AA, precursor to PGE2), and eicosapentaenoic acid (EPA, precursor to PGE3) on IL-2 production by PHA-stimulated human PBMC. DGLA and AA inhibited IL-2 production in a dose-dependent manner: half-maximal inhibition was obtained by using the fatty acids at the dose of 10 micrograms/ml without significant effects on cell viability. EPA inhibited IL-2 production by PBMC of only some donors. Incubation of cells in the presence of oleic, stearic, and palmitic acids, which are not PG precursors, did not affect mitogen-induced IL-2 production. A progressive increase in incorporation of DGLA into cellular lipids was observed over a 48-h incubation period. IL-2 production was reduced also when PBMC were pretreated overnight with DGLA or AA and washed before exposure to PHA. Whereas addition of the cyclo-oxygenase inhibitor, indomethacin, at the time of mitogenic stimulation led to increased IL-2 production and prevented mitogen- and fatty acid-induced increases in PGE release, it had no significant effect on the capacity of the fatty acids to suppress IL-2 production. Time course experiments showed that DGLA and AA inhibited IL-2 production even at times of minimal or no PGE release by the treated cultures. Moreover, DGLA and AA inhibited IL-2 production by the human leukemia T cell line Jurkat which, when appropriately induced, is able to release high levels of IL-2 in the absence of accessory cells and measurable PGE production. Taken together, these data indicate that essential fatty acids inhibit IL-2 production directly without conversion into their cyclo-oxygenase pathway products, and suggest that human lymphocyte function may be altered profoundly by small changes in their fatty acid profile.
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PMID:Prostaglandin E precursor fatty acids inhibit human IL-2 production by a prostaglandin E-independent mechanism. 254 87

Expression of major histocompatibility complex class II Ags HLA-DR, HLA-DP, and HLA-DQ on human BM granulocyte-erythroid-macrophage-megakaryocyte CFU (CFU-GEMM), BFU-E, and CFU-GM was examined by indirect immunofluorescence, cell sorting, and complement-mediated cytotoxicity. BM, highly enriched for progenitor cells by depletion of mature hematopoietic elements, was further separated by sterile sorting into HLA-DR (-), low, intermediate, and high intensity HLA-DR (+), as well as HLA-DP (+) and HLA-DP (-) cell fractions and assayed for progenitor cell content. In addition, in the case of HLA-DR, CFU-GM response to inhibition by prostaglandin E was determined. Cell sorting and cytotoxicity data confirm that approximately 95% of assayable erythroid, myeloid, and multipotential progenitor cells expressed HLA-DR, whereas HLA-DQ Ags were undetectable. HLA-DR and HLA-DP Ags were co-expressed on 61% of these progenitor cells, predominantly those expressing HLA-DR at high intensity. Day 7 and 14 CFU-GM showed a trend toward segregation to the high HLA-DR (+) cell fractions, especially when recombinant human G-CSF was used to stimulate clone formation. Both day 7 and day 14 CFU-GMs were found predominantly in the HLA-DP (+) cell fraction. In contrast, BFU-E and CFU-GEMM were found in the low intensity HLA-DR cell fraction and predominantly in the HLA-DP (-) fraction. Both eosinophil CFU and cells giving rise to basophil/mast cells in suspension culture were found in the low and intermediate intensity HLA-DR fractions, but could be segregated into HLA-DP (+) and HLA-DP (-) cell fractions, respectively. Functional analysis of day 7 CFU-GM segregated, based upon HLA-DR intensity, indicated a positive correlation between increasing HLA-DR intensity and responsiveness to inhibition by prostaglandin E. Furthermore, only those CFU-GM expressing HLA-DR at high intensity could be removed by cytolytic treatment using a mAb anti-HLA-DR previously shown to be selective for CFU-GM responsive to PGE and in S phase of the cell cycle.
Leukemia 1988 Oct
PMID:Differential expression of class II MHC antigens in subpopulations of human hematopoietic progenitor cells. 317 44

The behaviour of phagocytosis and that of PGE1 and PGE2 in the circulating granulocytes of normal and leukaemic subjects was investigated by the comparison of latex particles and the PAP (peroxidase-antiperoxidase) immuno-enzymatic method respectively. Generally speaking, it was found that chronic myeloid leukaemia and acute myeloblastic leukaemia were accompanied by a marked reduction in phagocyting capacity, whereas this is apparently normal in CLL and ALL. PCE values, on the other hand, were well down in lymphatic leukaemia, AML and AMML, but not in CML, where high PGE (especially PGE2) was noted both basally and after phagocytosis. That the PGE take part in phagocytosis is shown by their redistribution in phagocyting cells, with elective accumulation in the membrane and around the engulfed material.
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PMID:[Behavior of PGE1 and PGE2 in the granulocytes of normal and leukemic subjects during phagocytosis in vitro]. 695 84

With very few exceptions, it has not been possible to grow human myeloid cells for long periods in culture. We have recently developed techniques enabling the long-term in vitro propagation of normal immature myeloid cells from fresh foetal cord blood and monocytes from normal adult peripheral blood, and have utilized these procedures to initiate cultures of fresh peripheral blood leukocytes from leukemic donors. In four of 26 leukemic samples tested, leukocyte replication beyond that obtained in control cultures was observed, and in one of these HL-92, derived from the peripheral blood of a patient with acute myelomonocytic leukemia, the culture has continued to replicate slowly for over 2 years under the special growth conditions. Morphological, cytochemical, immunological and functional studies show that the culture consists predominantly of immature myeloid cells (myeloblasts through to myelocytes) but also contains some mature neutrophils and monocytes. At least a portion of HL-92 cells express Fc and complement receptors, contain histacompatibility locus antigens, including HLA-DR, and release GM-CSA, low levels of PGE and lysozyme. HL-92 cells can be induced with DMSO or RA to differentiate into mature neutrophils (an increase from 20 to 70% of the cell population) as determined by morphology, by an increase in phagocytic cells, and superoxide anion production. Fresh leukocytes from the patient's bone marrow appeared to have a diploid karyotype. However a consistent chromosomal abnormality observed in HL-92 was a deletion in the long arm of chromosome 11 [del(11)(q23)]. This is consistent with recent observations in monocytic leukemia. Since the few other established human myeloid cell lines have various chromosomal abnormalities, and some respond to differentiation inducers, while others do not, there appears to be no detectable common chromosome change required either for in vitro growth of myeloid cells or their response to inducers of differentiation. These cell lines and the application of the techniques described here for the growth of myeloid cells from other leukemic or normal sources should be helpful in the study of normal and leukemic myeloid cell growth and differentiation.
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PMID:Establishment, characterization and differentiation induction of a new human diploid myelomonocytic cell line (HL-92) derived from a patient with acute myelomonocytic leukemia. 696 Dec 68

This paper reports the results of our studies concerning the specificity and mechanism of anemia in tumor-bearing mice. Three different types of transplanted extramedullary tumors, including a carcinoma (EAC), a sarcoma (S-180), and a leukemia (L-1210) produced anemia, neutrophilia, and medullary erythroblastopenia. Because the most striking effects were observed with S-180, it was selected for detailed study. Although erythroblasts were greatly decreased in the bone marrow to about 1% in the differential count, CFU-E and BFU-E were not, suggesting inhibited maturation of erythroid progenitors. Suppression of MSC to 1/3 of normal occurred at 21 days of tumor bearing, and qualitatively abnormal MSC at 35 days failed to enhance CFU-E and BFU-E in split-phase culture. We found that these MSC from tumor-bearing mice produced suppressive levels of PGE. PGE production and erythroid colony enhancement of MSC from either normal or tumor-bearing mice was abrogated by including 5 micrograms/ml indomethacin in the split-phase culture. Medium conditioned by S-180 that was capable of suppressing the growth of MSC colonies had no direct effect on erythroid colony formation. Our results support a hypothesis that extramedullary tumors are capable of producing a lesion in the supportive tissue of the bone marrow, leading to anemia and medullary erythroblastopenia. We believe that early, the tumor suppresses the number of MSC required for maturation of erythroid precursors and later induces the normal numbers of MSC to produce suppressive levels of PGE.
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PMID:Prostaglandin E and the erythropoietic and stromal insufficiency induced by extramedullary tumor. 719 21

The behaviour of prostaglandins A, B, E 1, E 2, F 1 and F 2 has been examined in the granulocytes and lymphocytes of the peripheral blood of normal subjects and in circulating leucocytes of patients with CML, AML, CLL and ALL. At the same time, modifications of PGE 2 in the granulocytes of normal subjects and in patients with CML or AML before and after phagocytosis of latex particles were monitored. The general observation was a lowering in PGE and PGF in acute myeloid and lymphatic leukaemia, while the variations in CML and CLL were rather complex. Also observed was a reduction in PGE 2 in AML but not in CML, including a reduced response to phagocytosis in granulocytes. The data are compared with previous reports of AMPc and GMPc in the same cells and commented on, taking into consideration their possible reflexion on the proliferative and functional activity of the cells examined.
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PMID:[Behavior of several prostaglandins (PGA, PGB, PGE 1, PGE 2, PGF 1, PGF 2) in normal and leukemic leukocytes. Radioimmunological method on intact cells]. 724 9

Leukaemia inhibitory factor (LIF) is a pleiotrophic cytokine which plays an obligatory role in mouse implantation. To investigate its potential role in the regulation of uterine function in the human, LIF secretion by isolated human endometrial glandular epithelial and stromal cells in primary culture was determined. Endometrial cells secreted a detectable amount of LIF protein during the first 48 h of culture. In the follicular and late-luteal phases, LIF secretion by both cell types was low. At every stage of the menstrual cycle, the epithelial cells secreted significantly more LIF than did stromal cells. Glandular epithelial cells of the mid-luteal phase, at the expected time of implantation in the human, secreted significantly more LIF than at other stages of the cycle. Stromal cells showed a similar, but nonsignificant, LIF secretion pattern. It could be concluded that endometrial LIF expression was dependent on cell type and stage of the menstrual cycle, and might thus play a role in human implantation. Oestradiol-17 beta stimulated both prostaglandin (PG) F and E release by the epithelial cells in both follicular and luteal phases. PGE release during the luteal phase was greater than in the follicular phase. However, addition of recombinant human LIF did not change either PGF or PGE release in either follicular or luteal phases, in the presence or absence of oestradiol.
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PMID:Leukaemia inhibitory factor in human endometrium during the menstrual cycle: cellular origin and action on production of glandular epithelial cell prostaglandin in vitro. 765 Jan 42


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