Gene/Protein Disease Symptom Drug Enzyme Compound
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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)

Report of a T-cell rich B-cell lymphoma (TCRBCL) in a 43 years old man with an associated haemophagocytic syndrome (HS). At presentation the haemophagocytic cells involved the same organs as the lymphoma, i.e. spleen, liver, abdominal lymph nodes and bone marrow. As supportive measure to alleviate chemotherapy-induced granulocytopenia the cytokine granulocyte-macrophage colony-stimulating factor (GM-CSF) was given. After an initial improvement of the blood granulocyte count pancytopenia developed again, resulting in fatal sepsis. Autopsy demonstrated massive proliferation of macrophages in the bone marrow with haemophagocytosis as morphological correlation to the pancytopenia. The observation that exogenous GM-CSF enhanced the preexistent HS primarily reactive to the TCRBCL raises the question if endogenous GM-CSF may play a role in triggering a HS. The observed association of TCRBCL and HS has not been reported so far.
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PMID:[T-cell rich B-cell lymphoma associated with hemophagocytic syndrome]. 128 41

Thymus humoral factor-gamma 2 (THF gamma 2), an octapeptide important for T-lymphocyte regulation, was assessed for its effect on the in vitro growth of human hematopoietic progenitor cells. This was achieved using a recombinant granulocyte-macrophage colony-stimulating factor (rGM-CSF)-stimulated myeloid cell colony formation (granulocyte-macrophage colony-forming cells, GM-CFC) assay as well as a recombinant erythropoietin (rEpo)-stimulated erythroid burst formation (erythroid burst-forming units, BFU-E) assay. Cells were obtained from bone marrow (BM) and peripheral blood (PB) of normal healthy donors and from patients with suppressed bone marrows. The latter group included aplastic anemia, leukemia, and lymphoma patients and patients with solid tumors who responded to intensive chemotherapy with significant pancytopenia. THF gamma 2 significantly enhanced normal BM and PB GM-CFC and PB BFU-E by 2- to 2.5-fold. This effect was totally dependent on the presence of the respective growth factors, that is, rGM-CSF or rEpo, and was specifically reversed by an anti-THF gamma 2 antiserum. Furthermore, although THF gamma 2-induced enhancement of GM-CFC colony formation was not affected by lymphocyte or monocyte depletion, the augmenting effect of the peptide on BFU-E was completely abrogated in the absence of lymphocytes. THF gamma 2-induced augmented growth of progenitor cells derived from severely suppressed marrows was minimal. However, cells from moderately neutropenic patients with leukemia in remission or with lymphoma under chemotherapy responded to the peptide similarly to cells from normal donors. These results suggest a stimulatory role for THF gamma 2 on human myeloid and erythroid hematopoietic progenitor cells. They also suggest the lymphocyte dependence of BFU-E enhancement and lymphocyte independence of GM-CFC stimulation by THF gamma 2. In the former case the thymus-derived peptide may act through the induction of certain erythroid-enhancing lymphokines.
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PMID:Thymic humoral factor-gamma 2, an immunoregulatory peptide, enhances human hematopoietic progenitor cell growth. 154 85

We treated a patient with therapy-related myelodysplastic syndrome (MDS) with human recombinant granulocyte-macrophage colony-stimulating factor (GM-CSF) and erythropoietin (Epo). The patient achieved a hematological remission which continued for more than 16 months despite discontinuation of the treatment. Before the treatment with GM-CSF and Epo the patient had severe pancytopenia, required frequent red cell transfusions, and experienced episodes of severe infection, but after the therapy he no longer needed transfusion and no longer had the infection. While the patient remained in hematological remission, bone marrow examination revealed trilineage dysplasia, and cytogenetic analysis showed an abnormal karyotype [48, XY, +8, +der(1q5p)] in 100% of the metaphases examined. These findings suggest that the hematological remission of this patient may not result from the recovery of the non-clonal hematopoiesis of a normal clone, but result from the monoclonal hematopoiesis of a neoplastic clone.
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PMID:A hematological remission by clonal hematopoiesis after treatment with recombinant human granulocyte-macrophage colony-stimulating factor and erythropoietin in a patient with therapy-related myelodysplastic syndrome. 154 64

The regulation of haemopoiesis in myelodysplastic syndromes (MDS) was evaluated by measuring and comparing the in vitro response of marrow progenitors from 18 MDS patients to stimulation with recombinant haemopoietic growth factors (HGFs), granulocyte-macrophage colony-stimulating factor (GM-CSF), granulocyte CSF (G-CSF) and interleukin-3 (IL-3). A similar pattern of colony growth was detected with all three HGFs in most MDS patients, exhibiting subnormal growth of GM-CFU and markedly poor to absent growth of BFU-E and CFU-GEMM. A common severe impairment in the growth of all colony types with all three HGFs was observed in five patients, four of whom presented with pancytopenia. The stimulation of MDS marrow progenitors with a five-fold higher than control saturating dose of HGFs induced a significant increase in the frequency of one, two, or all three colony types in cultures of 14 patients, whereas colony numbers in control (n = 8) marrow cell cultures were not significantly changed. All four of the non-responders were pancytopenic and three exhibited markedly impaired colony growth. Supersaturating GM-CSF, G-CSF and IL-3 increased GM-CFU numbers in six, three, and three patients, respectively. The values for BFU-E were three, six, and seven and for CFU-GEMM two, one, and five. The enhancement of MDS marrow colony numbers by supersaturating HGFs which exert their effects directly or via the action of marrow accessory cells, suggests that the progenitor cell growth abnormalities in these disorders may involve a defect in the capacity of accessory and/or progenitor cells to respond to stimulation with specific haemopoietic growth regulators.
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PMID:Impaired response of myelodysplastic marrow progenitors to stimulation with recombinant haemopoietic growth factors. 170 45

The myelodysplastic syndromes are clonal hematopoietic stem cell disorders characterized by varying degrees of pancytopenia and often a progression to acute myeloid leukemia. Recent evidence has linked myelodysplastic syndromes to environmental and occupational genotoxic exposure. Specific cytogenetic abnormalities are well described in myelodysplastic syndromes and have been demonstrated to be useful diagnostic and prognostic tools. Activation of protooncogenes such as ras and fms have also been noted in myelodysplastic syndromes; however, their contribution to the pathogenesis of the syndrome remains to be determined. Aggressive leukemia-like induction therapy, differentiating agents (low-dose cytarabine, 13-cis-retinoic acid) have had little impact on overall survival in myelodysplastic syndromes. The recombinant hematopoietic growth factors (granulocyte-macrophage colony-stimulating factor, granulocyte colony-stimulating factor) may be of significant benefit to patients with myelodysplastic syndromes, although it remains to be determined whether they will have a substantial impact on survival. Allogeneic bone marrow transplantation is the only potentially curable treatment of myelodysplastic syndromes. The advanced age of these patients as well as the lack of histocompatible donors restricts this modality to only a small proportion of patients.
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PMID:Recent advances in biology and treatment of myelodysplasia. 171 May 5

Granulocyte-macrophage colony-stimulating factor (GM-CSF) is a multifunctional haematopoietin which can promote production of several blood cell lineages, though the predominant target cells are neutrophils, monocytes, and their precursors. Occasional undesirable clinical effects include eosinophilia, an increase in blasts, or thrombocytopenia. Here, we describe four patients who were treated with GM-CSF, at subcutaneous doses significantly lower than are conventional, and experienced an unusual response pattern. Three patients had severe pancytopenia associated with chronic lymphocytic leukaemia (CLL) or myelodysplastic syndrome (MDS) and exhibited an unexpected switch in the responsive lineage on high- versus very low-dose therapy. The two CLL patients developed marked eosinophilia (up to 10.0 x 10(9) cells/l) without an increase in neutrophils on 125-300 micrograms/m2/d of GM-CSF. In contrast, when the dose was lowered to 10 micrograms/m2/d, the neutrophils rose to physiological levels, without significant eosinophilia. The MDS patient showed a rapid rise in peripheral blasts (baseline level = 0; post-therapy level = 5.0 x 10(9)/l), without a change in other cell types, when receiving 60 micrograms/m2/d of GM-CSF. After GM-CSF was held, blasts returned to baseline levels; reinstituting therapy at the very low dose of 6 micrograms/m2/d was followed by an increase in platelet counts from 50 to 185 x 10(9)/l with only a minor increase in blasts. The fourth patient, who suffered from severe aplastic anaemia complicated by recurrent gastrointestinal haemorrhage, was only treated with the low-dose regimen. He showed a predominant platelet effect with counts rising from 9 to 169 x 10(9)/l. Very low-dose GM-CSF therapy was devoid of constitutional side effects. The biological implications of these GM-CSF responses are discussed. Our results indicate that, in some patients, GM-CSF may stimulate different target cells depending on the dose. Therefore, in contrast to the results of administration of many classical drugs, there may not always be a direct relationship between the amount of GM-CSF given and the optimal effect.
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PMID:Differential dose-related haematological effects of GM-CSF in pancytopenia: evidence supporting the advantage of low- over high-dose administration in selected patients. 187 20

Long-term bone marrow culture (LTBMC) for human hemopoiesis supports continuous proliferation and differentiation within the myeloid progenitor population by the formation of an adherent stromal monolayer. LTBMC represents the most suitable in vitro model for the study of regulatory mechanisms in human hemopoiesis. We investigated the effect of recombinant human granulocyte-macrophage colony-stimulating factor (rhuGM-CSF) on bone marrow of normal donors in LTBMC. The cells (2 x 10(6)/ml) were incubated with 100 ng/ml rhuGM-CSF for 24 h in culture medium supplemented with 10% fetal calf serum. After the preincubation, LTBMCs were started and maintained over a period of 10 weeks. After 1 week in culture we observed a statistically significant difference with a 1.5-fold higher number of nonadherent cells in the LTBMCs containing the bone marrow preincubated with rhuGM-CSF (p less than 0.05). This increase was due to an expansion of the mature myeloid cells. At the same time point the number of GM colony-forming units (CFU-GM)/ml in the LTBMCs with rhuGM-CSF-preincubated bone marrow was slightly increased compared to the controls without reaching a statistically significant level. We conclude that rhuGM-CSF at a saturation dose is a potent stimulator of in vitro myelopoiesis stem cell pool. This in vitro result is of relevance for the clinical use of rhuGM-CSF in patients undergoing bone marrow transplantation. The incubation of donor bone marrow prior to transplantation might be a new approach to facilitate the engraftment and to shorten the phase of pancytopenia.
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PMID:Enhanced myelopoiesis in long-term cultures of human bone marrow pretreated with recombinant granulocyte-macrophage colony-stimulating factor. 264 56

A complete hematologic remission was achieved in a patient with therapy-related preleukemia and transfusion-dependent pancytopenia after treatment with recombinant human granulocyte-macrophage colony-stimulating factor (GM-CSF). The patient remained in remission for nearly 1 year despite the discontinuation of GM-CSF treatment. Several lines of evidence suggest that normal hematopoiesis was restored after GM-CSF treatment. First, the cytogenetic anomaly, which was present before GM-CSF, completely disappeared after three cycles of treatment. Cytogenetic conversion was documented by conventional karyotypic evaluation of mitotic bone marrow cell preparations as well as by premature chromosome condensation analysis of the nonmitotic cells of bone marrow and peripheral blood. Second, the growth pattern and cycle status of bone marrow granulocyte-macrophage (CFU-GM) and erythroid (BFU-E) progenitor cells were found to be normal during remission. Third, X chromosome-linked restriction fragment length polymorphism-methylation analysis of DNA from mononuclear cells (greater than 80% lymphocytes) and mature myeloid elements showed a polyclonal pattern. These findings suggest that restoration of hematopoiesis in this patient after GM-CSF treatment may have resulted from suppression of the abnormal clone and a selective growth advantage of normal elements.
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PMID:Stimulation of nonclonal hematopoiesis and suppression of the neoplastic clone after treatment with recombinant human granulocyte-macrophage colony-stimulating factor in a patient with therapy-related myelodysplastic syndrome. 267 13

Aplastic anemia is a syndrome in which pancytopenia occurs in the presence of hypocellularity of the bone marrow. To assess the biologic activities of recombinant human granulocyte-macrophage colony-stimulating factor (GM-CSF) in aplastic anemia, we gave GM-CSF (60 to 500 micrograms per square meter of body-surface area) to 10 patients with moderate or severe disease, by continuous intravenous infusion daily for two weeks, and repeated the treatment after a two-week rest period. The treatment increased the white-cell count (1.6- to 10-fold) in all patients, primarily because of an increase in the numbers of neutrophils (1.5 to 20-fold), eosinophils (12- to greater than 70-fold), and monocytes (2- to 32-fold). Rates of hydrogen peroxide production in purified granulocyte fractions increased during GM-CSF treatment. Increases in bone marrow cellularity, myeloid precursor cells, and myeloid:erythroid cell ratios accompanied the white-cell response. Despite the in vivo response of the white-cells, the concentration of colony-forming cells remained the same. Measurable concentrations of interleukin-2 (2 to 15 units per milliliter) were found in the serum of 8 patients, and high levels of erythropoietin (81 to 1200 IU per liter) were found in 10 patients. The predominant side effects were constitutional symptoms. These results indicate that recombinant human GM-CSF is effective in stimulating myelopoiesis in patients with severe aplastic anemia and may benefit some patients in whom the disorder is refractory to standard forms of therapy.
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PMID:Stimulation of myelopoiesis in patients with aplastic anemia by recombinant human granulocyte-macrophage colony-stimulating factor. 305 91

A 6-year-old white male had a myelodysplastic syndrome (refractory anemia with excess blasts in transformation) and was treated with high dose chemotherapy. A combined esterase stain of the marrow blasts showed granulocytic differentiation. Subsequently, persistent pancytopenia with a severely hypocellular bone marrow developed, which was treated with a combination of granulocyte colony-stimulating factor and granulocyte-macrophage colony-stimulating factor. Sixteen days after the initiation of therapy, histologic examination of the bone marrow revealed a marked proliferation of histiocytes. To the best of the authors' knowledge, this is the first report of histiocytic proliferation in the bone marrow after colony-stimulating factor therapy.
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PMID:Bone marrow histiocytic proliferation in association with colony-stimulating factor therapy. 827 47


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