Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound

---

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

Granulocyte-macrophage colony stimulating factor (GM-CSF) is one of a number of lympho-haemapoietic cytokines, including CSF-1, interleukin-6 (IL-6) and leukaemia inhibitory factor (LIF) now known to be synthesized by epithelial cells in the murine uterus. GM-CSF synthesis is regulated primarily by the ovarian steroid hormone oestrogen, but is also subject to modulation by factors including a seminal component of seminal vesicle origin which stimulates a 20-fold increase in luminal fluid content at mating, and bacterial lipopolysaccharide (LPS) and the T-lymphocyte and natural killer (NK) cell product interferon-gamma (IFN gamma). In the non-pregnant mouse GM-CSF synthesis peaks at oestrus. Synthesis is maintained at comparable or moderately higher levels during the preimplantation period of pregnancy and in the non-decidualized endometrium during mid gestation. An embryotrophic activity is suggested by studies in vitro that indicate that GM-CSF stimulates attachment and outgrowth of blastocysts. It is postulated that GM-CSF is of major importance to the physiology of pregnancy through its role as a component of a local cytokine circuit acting to recruit and regulate function of endometrial leukocytes, and by its action as interlocutor and important effector arm in embryo-maternal interactions during gestation.
...
PMID:Granulocyte-macrophage colony stimulating factor (GM-CSF): one of a family of epithelial cell-derived cytokines in the preimplantation uterus. 146 94

During the myeloid blast crisis (BC) of chronic myelogenous leukaemia (CML) non-random additional chromosome abnormalities occur in over 80% of patients. However, these cytogenetic changes have been reported to precede the clinical signs of CML-BC by several months to years suggesting that other biological events may participate in the multistep process of acute transformation of CML. The autocrine production of growth factors has been recently shown to occur in several haematological malignancies and particularly in acute myeloblastic leukaemia (AML). In the present report we demonstrate that IL-1 beta gene is expressed in almost all cases of CML in myeloid blast crisis. The secretion of IL-1 from CML blasts in culture supernatants was confirmed in all five of the patients we studied. A high proportion of cases showed constitutive expression of the M-CSF gene and many of the same patients often had a simultaneous co-expression of the proto-oncogene c-fms which encodes for the M-CSF receptor. After exposure of leukaemic cells to phorbol myristate acetate (PMA), release of M-CSF protein was documented in three of five patients studied. No significant interleukin-3 (IL-3), granulocyte-macrophage colony-stimulating factor (GM-CSF) or granulocyte colony-stimulating factor (G-CSF), was detected in these patients demonstrating that a different pattern of growth factors secretion exist in AML and CML, where distinct molecular events are likely involved in the control of leukaemic proliferation.
...
PMID:Constitutive expression of IL-1 beta, M-CSF and c-fms during the myeloid blastic phase of chronic myelogenous leukaemia. 153 85

We have previously described differentiation associated tyrosine protein kinase activity in WEHI-3B monomyelocytic leukemia cells and have presented evidence which suggests that this activity may not be involved in the initiation of the differentiation process, but more likely has a functional role in the mature myeloid cell. The present study was undertaken in an attempt to identify the protein(s) responsible for the tyrosine protein kinase activity and to seek a potential role for this activity in the mature cell. We and others have detected the p92c-fes tyrosine protein kinase in WEHI-3B cells. This protein has been implicated in myeloid differentiation, as well as in the transduction of signals in response to granulocyte macrophage colony stimulating factor (GM-CSF). Thus, it was of interest to determine whether tyrosine phosphorylation may be involved in the response of WEHI-3B cells to GM-CSF. Treatment of differentiated WEHI-3B D+ cells with GM-CSF was found to result in the tyrosine phosphorylation of a number of endogenous cellular proteins in a concentration-dependent, rapid and transient manner. In contrast, the cytokine did not elicit such a response in undifferentiated cells, despite the fact that undifferentiated cells have been reported to possess GM-CSF receptors. These findings are consistent with the concept that the effects of GM-CSF on differentiated myeloid cells are mediated through tyrosine phosphorylation, that only differentiated cells are competent to accomplish this event, and that this response constitutes at least one functional role for the myeloid differentiation associated tyrosine protein kinase activity.
...
PMID:Differentiation stage specificity of tyrosine phosphorylation in response to granulocyte macrophage colony stimulating factor (GM-CSF). 155 4

DNA methylation belongs to the multilevel genetic control system regulating differentiation processes and gene expression. The extent to which DNA methylation contributes to the differentiation of hematopoietic cells is elusive. In the present study we investigated the methylation state of the c-fms/M-CSF receptor gene in normal human blood cells and tissue macrophages. The methylation pattern of the c-fms gene as detected by isoschizomeric restriction analysis with MspI/HpaII showed only slight interindividual variations in normal donors, whereas constant differences were found between granulocytes and monocytes from the same donor. The second intron of the c-fms gene contains several CpG loci which were found to be hypomethylated on both alleles in monocytes and tissue macrophages. By contrast, these positions were methylated in granulocytes and lymphocytes that did not express the c-fms gene. In comparison to monocytes alveolar and peritoneal macrophages revealed an enhanced demethylation. There were constant differences in c-fms gene methylation between alveolar and peritoneal macrophages with a higher degree of demethylation in alveolar macrophages. We conclude that c-fms gene demethylation is involved in the differentiation of monocytes and macrophages from immature precursors and that the demethylation of lineage-specific growth factor receptor genes might provide an important step in lineage commitment of hematopoietic cells.
Leukemia 1992 May
PMID:Lineage-specific methylation of the c-fms gene in blood cells and macrophages. 159 6

The human factor-dependent leukemia cell line UCSD/AML1 contains the t(3;3) (q21;q26) characteristic of the syndrome of acute leukemia with high platelets. The human homologue of the murine leukemia oncogene evi-1 was recently localized to chromosome 3q24-3q28 and transcription of evi-1 is a frequent event in mouse-retrovirus-induced leukemias (17). To determine whether translocations near human 3q24 might induce similar genetic changes, we examined and compared evi-1 and c-myc expression and regulation in UCSD/AML1 cells. Steady-state evi-1 transcripts were detected in UCSD/AML1 and murine leukemia M1 cells, but were not present in HL60 or Namalwa human leukemia cells. Transcription assays showed the evi-1 gene was actively transcribed in UCSD/AML1, but not HL60 nuclei. Evi-1 transcript sizes and half-life were similar in UCSD/AML1 and human HEC-1B carcinoma cells which express evi-1 transcripts, but do not have abnormalities involving chromosome 3. An alternative splice site detected by polymerase chain reaction was present in transcripts from both cell lines. Regulation of evi-1 RNA in UCSD/AML1 cells was similar to that of actin transcripts in response to cycloheximide or phorbol-ester-induced macrophage differentiation. After withdrawal of granulocyte/macrophage colony-stimulating factor (GM-CSF), evi-1, actin, and histone H3 transcripts declined in concert with exit from the cell cycle. Minor differences in rates of recovery were noted for these three genes after GM-CSF restimulation. In contrast, c-myc was expressed at high levels in UCSD/AML1 cells and showed evidence for specific regulation in response to cycloheximide, phorbol ester, and GM-CSF withdrawal and restimulation. These studies suggest the 3q translocation in UCSD/AML1 cells is associated with evi-1 transcription and expression of a potential transforming gene. In contrast to c-myc, evi-1 expression is minimally altered by biologically active chemicals or growth factor stimulation.
Leukemia 1992 May
PMID:Expression and regulation of the evi-1 gene in the human factor-dependent leukemia cell line, UCSD/AML1. 159 10

Exposure of 3 month old SJL/J mice to a single dose of 300 r yielded 15-30% acute myelomonocytic leukemia (AML) development at a mean latency of 1 year. Additional treatment with dexamethasone shortly after irradiation increased leukemia incidence to 50%. All tumors were characterized by a partial deletion of one allele of chromosome 2 and the same deletion was detected in bone marrow and spleen cells of most irradiated mice, irrespective of the development of the disease. The presence of potential leukemic cells (PLC) in mice 4 months after the leukemogenic treatment was confirmed by transplantation studies. In these experiments PLC transition into overt AML seemed to be dependent on their transfer into irradiated recipients. Thus, exposure to 300 r results in the initiation of potential leukemic cells. Experiments were conducted in order to explore the possible role of radiation, cytokines and different hemopoietic growth factors on PLC promotion to overt leukemia. Exposure to 300 r, beside PLC initiation, was found to trigger the production of IL-6 and CSF-1; the additional administration of dexamethasone further increased CSF-1 levels. In vivo administration of CSF-1 into mice carrying radiation-induced PLC was most effective in PLC promotion to overt AML development.
Leukemia 1992
PMID:Multiphase process involved in radiation induced murine AML. 160 7

Tumor necrosis factor-alpha (TNF-alpha), produced predominantly by activated monocytes/macrophages, inhibits leukemic cell growth and may contribute to a graft-versus-leukemia effect after marrow transplantation. We examined the recombinant cytokines interferon (IFN)-alpha, IFN-gamma, granulocyte- macrophage colony-stimulating factor (GM-CSF), and macrophage colony-stimulating factor (M-CSF), alone or in combination, for their ability to induce monocytes from normal donors and patients after marrow grafting to express TNF-alpha mRNA and secrete TNF-alpha bioactivity. Monocytes were isolated from peripheral blood by Percoll separation of E-rosette-negative cells, and cultured with cytokines under non-adherent, endotoxin-free conditions. TNF-alpha transcripts were undetectable in freshly isolated monocytes from normal donors. Only the combination of IFN-gamma/GM-CSF was consistently capable of inducing substantial TNF-alpha mRNA transcript levels and protein secretion. Levels of TNF-alpha transcripts induced by IFN-gamma/GM-CSF were maintained for at least 36 h, in contrast to lipopolysaccharide (LPS) stimulation which caused TNF-alpha mRNA levels to peak after 2 h and decline rapidly thereafter. IFN-gamma/GM-CSF was also capable of inducing a prolonged (at least 48 h) secretion of TNF-alpha bioactivity. In contrast, greater than 80% of the total TNF-alpha bioactivity secreted by LPS-stimulated monocytes was secreted in the first 8 h. When monocytes were incubated with IFN-gamma alone ('priming'), washed and then exposed to GM-CSF, both TNF-alpha mRNA expression and TNF-alpha protein production occurred.(ABSTRACT TRUNCATED AT 250 WORDS)
...
PMID:Regulation of tumor necrosis factor-alpha production and gene expression in monocytes. 161 21

Acute myelomonocytic leukemia develops in 10-30% of irradiated (300 rad) SJL/J mice, after a lag period of around one year. Additional treatment with dexamethasone shortly after irradiation increased leukemia incidence up to 50%. Experiments were conducted in order to demonstrate the existence of preleukemic cells in irradiated mice and to explore the possible role of dexamethasone, cyclophosphamide, and different hemopoietic growth factors on their promotion to overt leukemia. Transplantation of bone marrow cells from mice exposed to 300 rad plus dexamethasone into appropriate recipients, performed 4-5 months after leukemogenic treatment, resulted in acute myeloid leukemia (AML) development of donor origin in 70% of the recipients. Transfer of fractionated preleukemic bone marrow showed that the highest AML incidence developed in the recipients of fractions enriched in early hemopoietic precursors. The promoting effect of dexamethasone on preleukemic cells was confirmed by demonstrating its similar coleukemogenic effect whether administered within several hours or 130 days after radiation. Treatment with cyclophosphamide shortly after radiation could not replace the dexamethasone effect but was found to be complementary to the coleukemogenic effect of dexamethasone. Early administration of hemopoietic growth factors (starting 14 days after radiation and dexamethasone) showed that colony-stimulating factor (CSF) 1 increased the AML incidence (75%) and reduced its latency. Treatment with recombinant granulocyte-CSF (rG-CSF) had a reduced effect and recombinant granulocyte-macrophage CSF (rGM-CSF) had no promoting effect. However, administration of different factors several months after the leukemogenic treatment revealed that rGM-CSF increased AML incidence (75%) and shortened its latency, whereas rG-CSF and CSF-1 had no effect. In contrast, the late administration of recombinant interleukin 6 reduced AML incidence significantly (23%). The present results indicate that murine radiation induced AML is a multiphase process involving radiation induced preleukemia that can be promoted by different treatments.
Leukemia 1992 Jul
PMID:Initiation and promotion in radiation-induced myeloid leukemia. 162 87

We have previously shown that total T cells derived from lymph nodes (LN) involved by Hodgkin's disease (HD) secrete higher levels of colony-stimulating activity than total T cells present within benign hyperplastic (BH) LN and B-non-Hodgkin's lymphoma (B-NHL) LN, suggesting that T cells with particular properties accumulate in HD LN. To further characterize this T-cell population, we have quantified production of both granulocyte-macrophage colony-stimulating factor (GM-CSF) and macrophage colony-stimulating factor (M-CSF) production in a total of 98 T-cell clones (TCC) derived from CD25+ activated T cells present in HD LN; TCC derived from CD25+ T cells obtained from B-NHL LN(101 TCC), BH LN(95 TCC), and peripheral blood (PBL; 38 TCC) of healthy donors were used as controls. HD LN were characterized by the presence of an elevated number (44%) of TCC producing particularly high titers of both GM-CSF and M-CSF, whereas only a minority of such TCC was found in control groups (10% in B-NHL, 16% in BH, 8% in PBL). These observations support the hypothesis of a selection of T-cell families with particular properties occurring in contact with Reed-Sternberg (RS) cells. According to the biological properties of GM-CSF and M-CSF, it seems reasonable to suggest the involvement of this particular subset of T cells in the granulomatous process, the peripheral blood polynucleosis, and in the paracrine growth of RS cells.
Leukemia 1992 Aug
PMID:Accumulation of T-cell clones producing high levels of both granulocyte-macrophage and macrophage colony-stimulating factors (CSF-1) in lymph nodes involved by Hodgkin's disease. 164 Jul 35

In this study we demonstrate that tumor necrosis factors (TNF alpha and TNF beta) are potent modulators of the in vitro proliferation of human AML cells. Blast cells from 11 cases of acute myeloblastic leukemia (AML) were incubated with recombinant TNF alpha or TNF beta in serum-free 3H-TdR uptake and colony culture systems in the presence or absence of recombinant interleukin-3 (IL-3), granulocyte macrophage colony-stimulating factor (GM-CSF), G-CSF, or M-CSF. Depending on the supplemented CSF, TNF could upregulate or suppress AML blast proliferation. Enhancement of AML growth by TNF was observed in the presence of IL-3 (in 9 of 11 cases in 3H-TdR assay; 6 of 9 cases in colony assay) and GM-CSF (in 8 of 11 cases in 3H-TdR assay; 4 of 9 cases in colony assay). In certain cases in which IL-3 or GM-CSF alone was unable to induce proliferative responses of AML cells, the simultaneous addition of TNF elicited colony growth and DNA synthesis suggesting a synergistic action between TNF and IL-3 or GM-CSF. In contrast, TNF suppressed G-CSF-induced growth (9 of 10 cases in 3H-TdR assay; 5 of 6 cases in colony assay). TNF could also stimulate DNA synthesis (in 2 of 11 cases) or colony formation (in 2 of 9 cases) in AML cultures without the addition of other growth factors. Experiments with neutralizing antibodies and specific radioimmunoassays for individual CSFs showed that the synergistic and antagonistic effects of TNF on AML growth could not be attributed to a release of one of these CSFs by the AML cells. The opposing consequence of exposure of AML blasts to TNF are of interest in view of our understanding of the pathophysiology of AML growth and the in vivo application of recombinant cytokines in AML patients.
Leukemia 1990 Jan
PMID:Modulation of colony stimulating factor-(CSF) dependent growth of acute myeloid leukemia by tumor necrosis factor. 168 38


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

---