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Query: UNIPROT:P04141 (granulocyte-macrophage colony-stimulating factor)
 6,790 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

With 214 subclones of the BALB/c myelomonocytic leukemia WEHI-3B, the granulocyte-macrophage colony-stimulating factor (GM-CSF) in impure or purified form, consistently increased the proportion of colonies exhibiting partial or complete differentiation in agar cultures. GM-CSF also increased colony size and content of daughter colony-forming cells. Serial recloning of WEHI-3B colonies in the presence of GM-CSF showed that when colonies differentiated completely, self-replication of the colony-forming cell was suppressed (clonal extinction). However, WEHI-3B cells exhibited clonal instability and even in the continuous presence of GM-CSF many colony-forming cells still generated cells able to form undifferentiated colonies. It appears unlikely that GM-CSF can completely suppress the progressive proliferation of a myeloid leukemic population of the WEHI-3B type.
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PMID:Clonal analysis of the action of GM-CSF on the proliferation and differentiation of myelomonocytic leukemic cells. 31 7

We studied the effects of D-factor on the growth of leukemic blast progenitors from 15 patients with acute myeloblastic leukemia and two leukemia cell lines in methylcellulose and suspension cultures. When stimulated by granulocyte colony-stimulating factor (G-CSF), granulocyte-macrophage colony-stimulating factor or interleukin-3, leukemic blast progenitors undergo terminal division with limited differentiation in methylcellulose culture, forming blast colonies. Leukemic blast progenitors can renew themselves. The self-renewal can be detected as secondary colony formation after replating primary blast colonies in fresh methylcellulose media and by the growth of clonogenic cells in suspension culture. D-Factor suppressed primary and secondary colony formation in methylcellulose culture. Furthermore, D-factor suppressed clonogenic cell recovery in suspension culture. The suppression by D-factor of the growth of leukemic blast progenitors was not significantly dependent upon the colony-stimulating factors used as growth-stimulating factors. High concentration of G-CSF did not overcome the suppressive effect of D-factor. The results indicate that D-factor is effective in suppressing not only terminal division but also self-renewal of leukemic blast progenitors.
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PMID:Effect of recombinant human D-factor on the growth of leukemic blast progenitors from acute myeloblastic leukemia patients. 128 10

In previous studies on patients with juvenile chronic myelogenous leukaemia (JCML), we found excessive proliferation of malignant monocyte-macrophage elements in the absence of exogenous growth factor, and impaired growth of normal haematopoietic progenitors. In the current study, six newly-diagnosed JCML patients were investigated to characterize the disease further. In co-cultures, JCML cell culture supernatant as well as patient plasma obtained at diagnosis produced a striking reduction in numbers of control marrow BFU-E, CFU-GM, CFU-Meg and CFU-GEMM colonies. Monoclonal anti-tumour necrosis factor alpha neutralizing antibodies (anti-TNF-alpha Ab) abolished these inhibitory properties. In sharp contrast, JCML supernatants exerted a marked growth-promoting effect on autologous JCML cells cultured in clonogenic assays. Anti-TNF-alpha Ab and anti-granulocyte-macrophage colony-stimulating factor neutralizing antibodies (anti-GM-CSF Ab) both reversed the stimulating effect. Recombinant GM-CSF and recombinant TNF alpha produced a profound increase in JCML colonies when tested individually and anti-GM-CSF Ab reversed the TNF-alpha effect. Expression studies of TNF-alpha and TNF-alpha receptor genes of cultured JCML cells demonstrated mRNAs for both. Further, TNF-alpha activity was assayed in a wide variety of cell culture supernatants and in normal and patients' plasma, and only the JCML specimens showed increased TNF-alpha values. Recombinant interleukin-1 alpha (IL-1 alpha) also stimulated JCML colony growth, but polyclonal anti-IL-1 neutralizing antibodies did not suppress JCML colony numbers nor did it reverse the effects of TNF-alpha or GM-CSF. The evidence indicated that the JCML monokine which inhibits normal haematopoiesis is TNF-alpha and that the endogenously-produced TNF-alpha and GM-CSF from JCML cells play an important role in the pathogenesis of the disease by acting as autocrine growth factors. IL-1 alpha also stimulates JCML cell proliferation as an accessory factor and augments the effect of GM-CSF, TNF-alpha or both.
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PMID:Central role of tumour necrosis factor, GM-CSF, and interleukin 1 in the pathogenesis of juvenile chronic myelogenous leukaemia. 131 Nov 95

Recombinant human tumor necrosis factor-alpha (TNF-alpha) was found to stimulate the growth of CMK, a human megakaryoblastic leukemia cell line. This stimulatory effect of TNF-alpha was blocked by anti-TNF-alpha antibody, but antibodies to recombinant human interleukin 3, granulocyte-macrophage colony-stimulating factor and interleukin 6 (all growth factors for CMK cells) did not reduce the stimulatory effect of TNF-alpha. Scatchard analysis showed that CMK cells expressed TNF-alpha receptors on the cell surface. The growth of CMK cells was also stimulated by lymphotoxin, which shares the same receptor as TNF-alpha. These results suggest that TNF-alpha stimulated the growth of CMK cells directly via its specific receptor.
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PMID:Stimulatory effect of tumor necrosis factor-alpha on the growth of CMK, a human megakaryoblastic leukemia cell line. 131 36

Phosphoinositol turnover, diacylglycerol generation, protein kinase C (PK-C) activity, and intracellular cyclic nucleotides were studied in an established human leukemia cell line, HL-60, in response to one of the hematopoietic cytokines, granulocyte-macrophage colony-stimulating factor (GM-CSF). Continuous exposure of HL-60 cells to GM-CSF induced the cell differentiation that was evaluated by the nitroblue tetrazolium (NBT) reducing activity. GM-CSF also exhibited a proliferative effect on HL-60 cells. GM-CSF at 1 nmol/L, an optimal concentration for cell growth and cell differentiation, induced significant changes in the intracellular inositoltriphosphate (IP3). Diacylglycerol generation was also stimulated by GM-CSF treatment. GM-CSF increased the membrane PK-C activity by 10-fold of the control, whereas no measurable change in cyclic nucleotides was observed. These data indicated that phosphoinositol turnover and the activation of PK-C were included in the GM-CSF signal transducing pathway in HL-60 cell. Phosphoinositol response leading to PK-C activation may act as a trigger signal of cell differentiation by GM-CSF.
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PMID:Stimulation of phosphoinositol turnover and protein kinase C activation by granulocyte-macrophage colony-stimulating factor in HL-60 cells. 132 43

The possibility that umbilical cord and placental blood from an HLA-identical sibling might produce stable donor-derived lymphohematopoietic engraftment was tested in a patient with juvenile chronic myelogenous leukemia (JCML). After conditioning with high-dose busulfan and cyclophosphamide, cryopreserved umbilical cord blood, containing 0.5 x 10(8) nucleated cells/kg and 2.7 x 10(4) colony forming units-granulocyte, macrophage (CFU-GM)/kg, was infused. A leukocyte count greater than 1,000/microL, absolute neutrophil count (ANC) greater than 500/microL, and platelet count greater than 20,000/microL (untransfused) were observed on days 39, 39, and 47 after transplantation, respectively. Donor cell engraftment was documented in the peripheral blood and bone marrow by cytogenetic analysis, restriction fragment length polymorphism (RFLP), and polymerase chain reaction (PCR) as early as day 21. Furthermore, the donor origin of each lymphohematopoietic lineage (ie, CD5+ T cells, CD19/20+ B cells, CFU-GM, and burst-forming unit-erythrocyte [BFU-E]) was confirmed. On day 200, assays of the peripheral blood and bone marrow showed an abnormal proliferation of CFU-GM at low seeding densities in the absence of exogenous growth factors, as well as a hypersensitivity to granulocyte-macrophage colony-stimulating factor (GM-CSF), both pathophysiologic characteristics of JCML. Recurrent disease was confirmed histologically on day 225. Together, these results demonstrate that umbilical cord blood contains sufficient numbers of hematopoietic stem cells necessary for the engraftment of leukemia patients treated with myeloablative therapy and that the detection of "spontaneous" CFU-GM and hypersensitivity to GM-CSF after treatment is a marker of residual or recurrent disease in patients with JCML.
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PMID:Transplantation of umbilical cord blood after myeloablative therapy: analysis of engraftment. 152 Aug 88

High-dose therapy with autologous marrow support results in durable complete remissions in selected patients with relapsed lymphoma and leukemia who cannot be cured with conventional dose therapy. However, substantial morbidity and mortality result from the 3- to 6-week period of marrow aplasia until the reinfused marrow recovers adequate hematopoietic function. Hematopoietic growth factors, particularly used after chemotherapy, can increase the number of peripheral blood progenitor cells (PBPCs) present in systemic circulation. The reinfusion of PBPCs with marrow has recently been reported to reduce the time to recovery of adequate marrow function. This study was designed to determine whether granulocyte-macrophage colony-stimulating factor (GM-CSF)-mobilized PBPCs alone (without marrow) would result in rapid and reliable hematopoietic reconstitution. Sixteen patients with metastatic breast cancer were treated with four cycles of doxorubicin, 5-fluorouracil, and methotrexate (AFM induction). Patients responding after the first two cycles were administered GM-CSF after the third and fourth cycles to recruit PBPCs for collection by two leukapheresis per cycle. These PBPCs were reinfused as the sole source of hematopoietic support after high doses of cyclophosphamide, thiotepa, and carboplatin. No marrow or hematopoietic cytokines were used after progenitor cell reinfusion. Granulocytes greater than or equal to 500/microL was observed on a median of day 14 (range, 8 to 57). Transfusion independence of platelets greater than or equal to 20,000/microL occurred on a median day of 12 (range, 8 to 134). However, three patients required the use of a reserve marrow for slow platelet engraftment. In retrospect, these patients were characterized by poor baseline bone marrow cellularity and poor platelet recovery after AFM induction therapy. When compared with 29 historical control patients who had received the same high-dose intensification chemotherapy using autologous marrow support, time to engraftment, antibiotic days, transfusion requirements, and lengths of hospital stay were all significantly improved for the patients receiving PBPCs. Thus, autologous PBPCs can be efficiently collected during mobilization by chemotherapy and GM-CSF and are an attractive alternative to marrow for hematopoietic support after high-dose therapy. The enhanced speed of recovery may reduce the morbidity, mortality, and cost of high-dose treatment. Furthermore, PBPC support may enhance the effectiveness of high-dose therapy by facilitating multiple courses of therapy.
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PMID:Mobilization of peripheral blood progenitor cells by chemotherapy and granulocyte-macrophage colony-stimulating factor for hematologic support after high-dose intensification for breast cancer. 135 Feb 29

The role of CD11/CD18 leukocyte adhesion molecules and their ligands in mediating non-major histocompatibility complex (MHC) restricted lymphocyte cytotoxicity is controversial. In order to examine the role of target cell intercellular adhesion molecule-1 (ICAM-1; CD54), a ligand of lymphocyte function-associated antigen (LFA-1) (CD11a/CD18), we exposed the human leukemia cell line, HL-60, to a variety of agents implicated in modulating ICAM-1 expression and/or sensitivity to lymphocyte cytolysis. Exposure of HL-60 cells to retinoic acid (RA), interferon (IFN)-alpha, IFN-beta, and IFN-gamma induced protection from lymphokine-activated killer (LAK) cytolysis. Only RA and IFN-gamma induced ICAM-1 expression. Tumor necrosis factor and vitamin D3, which also induced ICAM-1 expression, increased HL-60 sensitivity to LAK lysis. Granulocyte-macrophage colony-stimulating factor also increased sensitivity to LAK lysis; ICAM-1 was not induced. The state of cellular differentiation and expression of class I and II MHC antigens also did not correlate with sensitivity to LAK cytolysis. Exposure of untreated HL-60 cells and HL-60 cells expressing ICAM-1 to monoclonal antibody (mAb) versus ICAM-1 did not modulate LAK sensitivity. Exposure of LAK cells to mAb versus LFA-1 partially inhibited cytolysis; mAb versus CD18 inhibited cytolysis more completely. HL-60 cells were resistant to natural killer lysis; exposure to the various experimental agents did not alter sensitivity. We conclude that leukemic cell sensitivity to LAK cytolysis can be modulated by a variety of agents. Although our results suggest a role for leukocyte CD11/CD18 adhesion molecules in LAK cytolysis, the poor correlation between ICAM-1 expression and sensitivity to LAK lysis suggest that interactions other than LFA-1/ICAM-1 conjugation may be more central to the processes involved.
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PMID:Modulation of leukemic cell sensitivity to lymphokine-activated killer cytolysis: role of intercellular adhesion molecule-1. 136 53

Characteristics of hemopoietic-supportive (MS-1 and MS-5) and non-supportive (MS-K) cell lines were compared. Supportive cells adhered to hemopoietic stem cells and produced granulocyte-macrophage colony-stimulating factor (GM-CSF), whereas non-supportive cells did not adhere to hemopoietic cells and only produced macrophage colony-stimulating factor. Both cell lines produced substantial levels of IL-6 and steel factor (SLF) which is reportedly a stem-cell factor. Northern blot analysis revealed that SLF but neither c-kit nor interleukin 3 (IL-3) mRNA was detectable in these cell lines, although IL-3-like activity was found in the supernatant of MS-5 cell culture. These observations suggest that the hemopoietic-supportive function of stromal cells may reside in adherence of stem cells, and production of GM-CSF probably in combination with SLF. SLF may be transferred from stromal cells directly to stem cells through adhesion of stem cells to supportive stromal cells.
Leukemia 1992 May
PMID:Characterization of murine hemopoietic-supportive (MS-1 and MS-5) and non-supportive (MS-K) cell lines. 137 98

The blast cells from some patients with acute myeloblastic leukemia (AML) proliferate autonomously in vitro. We have previously identified four groups of AML blasts based upon their growth characteristics in vitro, in particular the degree of autonomous growth. We have now measured the production of granulocyte-macrophage colony-stimulating factor (GM-CSF) and interleukin-1 beta (IL-1 beta) by AML cells with different growth characteristics, using two sensitive enzyme-linked immunosorbent assays. Our results show a correlation between the capacity of AML blasts to produce GM-CSF and IL-1 beta and the ability to grow autonomously in vitro. Blasts from cells with no autonomous growth (n = 5) secreted low or undetectable amounts of GM-CSF and IL-1 beta. Blasts with totally autonomous growth (n = 10) secreted the highest levels of GM-CSF (mean 2469 pg/10(3) cells) and IL-1 beta (mean 3156 pg/10(6) cells). Whereas blasts with partially autonomous growth (n = 9) secreted intermediate levels of GM-CSF (mean 270 pg/10(6) cells) and IL-1 beta (mean 931 pg/10(6) cells). In order to determine whether GM-CSF production was autocrine or the consequence of paracrine secretion by differentiated leukemic cells, we studied the degree of autonomous growth and production of GM-CSF by CD34-positive blasts from eight patients whose unfractionated cells produced GM-CSF. We found that CD34-positive blasts from six of these cases grew autonomously to a degree comparable to that of the unfractionated cells, and that CD34-positive blasts produced GM-CSF either autonomously or in response to recombinant IL-1 beta. Our data suggests that in the majority of cases, CD34-positive blasts are capable of autonomous growth and autocrine GM-CSF production, however this is variably regulated by the paracrine production of IL-1 beta by CD34-negative cells.
Leukemia 1992 Jun
PMID:Role of autocrine and paracrine production of granulocyte-macrophage colony-stimulating factor and interleukin-1 beta in the autonomous growth of acute myeloblastic leukaemia cells--studies using purified CD34-positive cells. 137 78


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