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

An in vitro hematopoietic microenvironment was established from explained fragments of bone marrow from adult noninbred NIH Swiss mice with the use of corticosteroid-reconstituted horse serum. Infection with Kirsten murine sarcoma virus (Ki-MuSV) with either a Rauscher murine leukemia virus (R-MuLV) or Balb:virus-1 helper virus coat reduced proliferation of granulocytic and pluripotent hematopoietic stem cells and produced neoplastic transformation of both macrophages and preadipocytes in the adherent cell population within a 4-week period. Ki-MuSV-transformed, virus-releasing macrophages formed clusters of 4-49 cells in 0.8% methylcellulose-containing medium in the absence of added colony-stimulating factor (CSF), synthesized lysozyme, ASD-chloroacetate substrate-specific esterase-M, and CSF, and produced tumors following inoculation iv into adult NIH Swiss mice or ip into newborn NIH Swiss mice. In cultures infected with helper leukemia viruses R-MuLV or Balb:virus-1, gradual transformation of a distinct cell phenotype was observed over a 9-week period with generation of increasing numbers of atypical myeloblasts and promyelocytes which showed dyssynchronous nuclear-cytoplasmic maturation, basophilic granulation, cytoplasmic vacuolation, and formation of incompletely maturing CSF-dependent granulocyte-macrophage colonies in vitro and small spleen colonies in vivo. These data demonstrated that rapid biologic expression of the murine sarcoma virus genome in specific adherent "stromal" marrow cells prevents detection of a more subtle helper-virus-induced dysmyelopoiesis in a distinct nonadherent cell population.
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PMID:Phenotypically distinct target cells for murine sarcoma virus and murine leukemia virus marrow transformation in vitro. 21 35

BALB/c mice bearing the transplanted lymphoid tumour ABE-8 developed increased levels of neutrophil, macrophage and eosinophil progenitor cells in the marrow and spleen. Neutrophil-macrophage progenitors, assayed as granulocyte-macrophage colony-forming cells in agar, increased in number only if invasion of the marrow or spleen by ABE-8 cells was demonstrable. Rises in B-lymphocyte colony-forming cells occurred whether or not there was invasion of the host spleen or marrow. No increase in progenitor cells was found in mice bearing diffusion chambers containing ABE-8 cells. The magnitude of leukaemic infiltration was determined by assaying numbers of leukaemic stem cells in the spleen and marrow using a selective cloning system. This transplanted lymphoid leukaemia appears to be a useful model for analysing the effects of haemopoietic tumours on host haemopoietic tissues.
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PMID:Haemopoietic progenitor-cell responses in mice with the transplanted lymphoid leukaemia ABE-8. 31 15

Haemopoietic cells from patients with leukaemia and aplastic anaemia were studied in vitro with a standard soft agar tissue culture method. In the leukaemic patients a range of growth patterns was observed, but in most cases the results indicated that leukaemic cells retain the capacity to proliferate in response to the normal physiological neutropoieic regulator, colony-stimulating factor. In some patients, cells were apparently also capable of normal morphological maturation. These findings support the work of others in suggesting that leukaemic cells may be induced to behave normally in vitro, at least in some cases, raising possibilities of radically altered approaches to further therapy. In aplastic anaemia granulocyte-macrophage progenitor cells are greatly diminished.
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PMID:Local experience with granulocyte-macrophage progenitor cells in human leukaemia and aplastic anaemia. 31 59

Standardized culture of bone marrow in soft agar permits the detection of a population of granulocyte-macrophage progenitor cells (CFU-c). A spectrum of qualitative abnormalities serves to distinguish myeloid leukemic CFU-c from normal and remission populations. These abnormalities in maturation and proliferation are diagnostic of a myeloid leukemic state and serve to functionally reclassify acute myeloid leukemia at diagnosis into a number of categories based on in vitro growth pattern. The virtue of this classification is that it permits detection of a substantial number of patients who are refractory to conventional remission induction protocols. The clear distinction between normal and leukemic growth in vitro permits early detection of emerging remission CFU-c during induction therapy and of early onset of relapse in patients who are otherwise in complete remission. In patients with leukemia undergoing allogeneic bone marrow engraftment, marrow culture has proved of value in documenting the reconstitution of the patient and in detecting re-emergence of the original leukemic stem line prior to its detection by cytogenetic and hematological techniques. Serial studies on patients with chronic myeloid leukemia have allowed early diagnosis of blastic transformation and classification of blastic phase disease on the basis of in vitro growth pattern has revealed a similar spectrum of in vitro abnormalities as seen in AML. The cloning of normal or leukemic human myeloid progenitor cells (CFU-c) in agar or methylcellulose has permitted analysis of both quantitative and qualitative changes in this cell compartment in leukemia and other myelodysplastic states (1-7). Among these changes are abnormalities in maturation of leukemic cells in vitro (4, 5, 6), defective proliferation as measured by colony size or cluster to colony ratio (5, 6), abnormalities in biophysical characteristics of leukemic CFU-c (4, 5), regulatory defects in responsiveness to positive and negative feedback control mechanisms (8, 9) and the existence of cytogenetic abnormalities in vitro (10, 11). Detection of this spectrum of abnormalities has proved of clinical utility in diagnosis of leukemia and preleukemic states (5, 6, 12), in classification of leukemias and myeloproliferative diseases (5, 6), in predicting remission prognosis and response to therapy (5, 13), in predicting onset of remission or relapse in AML (13) and in monitoring the progression of chronic myeloid leukemia or preleukemic disease (4, 14). The present communication serves to illustrate the clinical applications of bone marrow culture in these various areas.
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PMID:Clinical utility of bone marrow culture. 79 48

Sera of 25 healthy controls and 75 patients suffering from myelodysplastic syndromes (MDS) were investigated for serum concentration of interleukin-1 alpha (IL-1 alpha), IL-3, IL-6, granulocyte-colony-stimulating factor (G-CSF), granulocyte-macrophage-CSF (GM-CSF), erythropoietin (Epo), and tumor necrosis factor-alpha (TNF-alpha). According to French-American-British (FAB) classification, 21 refractory anemia (RA), seven refractory anemia with ring sideroblasts (RARS), 15 chronic myelomonocytic leukemia (CMML), 12 refractory anemia with excess of blasts (RAEB), and 20 RAEB in transformation (RAEBt) were examined. TNF-alpha levels were inversely correlated with lower levels of hemoglobin concentration (r = -0.31, p = 0.005), irrespective of the requirements for transfusion in anemic MDS patients. Significant differences in TNF-alpha levels between CMML (26.2 +/- 5.9 pg/ml) and the FAB subgroups (16.1 +/- 1.6 pg/ml) were detected. There was an overall inverse relationship between the level of erythropoietin and the degree of anemia, but a wide range of Epo response between patients with similar hemoglobin concentrations. Serum levels of IL-1 alpha and GM-CSF were undetected in most of the patients. In 57% of the samples there were detectable levels of G-CSF, without a correlation of the serum levels with blood cell counts, nor with any of the FAB subcategories. Overall, 29% and 25% of the patient sera exhibited elevated IL-3 and IL-6 levels, respectively. There was no correlation of the serum levels with any of the blood counts, other cytokines, nor FAB subcategories. In conclusion, simple negative feedback mechanism between a specific cytokine and the production of blood cells seems not to be the case in MDS, except for red cell production and erythropoietin concentration. Our data may suggest the involvement of TNF-alpha in the pathogenesis of anemia in MDS.
Leukemia 1992 Dec
PMID:Measurement of serum cytokine levels in patients with myelodysplastic syndromes. 128 Jul 51

The effects of tumor necrosis factor-alpha (TNF-alpha) on feline bone marrow hematopoietic progenitors were evaluated by exposing bone marrow mononuclear cells from specific pathogen-free cats to different concentrations of TNF-alpha (ranging from 50 to 800 pg/ml) for 2 h before plating for clonal assays of colony-forming units. TNF-alpha caused a dose-dependent suppression of feline erythroid colony-forming units (CFU-E) and erythroid burst-forming units (BFU-E), whereas granulocyte-macrophage colony-forming units (CFU-GM) were minimally affected. TNF-alpha concentrations as low as 200 pg/ml significantly inhibited growth of erythroid progenitors. Addition of polyclonal rabbit anti-TNF-alpha antibodies completely neutralized the suppressive effect of TNF-alpha on erythroid progenitors. At higher concentrations of TNF-alpha (800 pg/ml), 35% of CFU-E and 21% of BFU-E still survived, indicating that some erythroid progenitors are not sensitive to a single exposure of TNF-alpha in vitro. These results suggest that TNF-alpha may play a role in regulating hematopoiesis in cats and may be involved in the pathogenesis of erythroid aplasia in cats infected with feline leukemia virus.
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PMID:Effects of tumor necrosis factor-alpha on normal feline hematopoietic progenitor cells. 132 Oct 52

Marrow stromal fibroblasts (FBs) likely play an important role in the regulation of hematopoiesis within the marrow microenvironment. Infection of these cells by feline leukemia virus (FeLV) might not only contribute to the pathogenesis of FeLV-induced hematologic diseases, but could provide a reservoir for virus in the infected cat. To determine the frequency of FeLV infection among marrow FB precursor cells (fibroblast colony-forming units, CFU-F) of cats viremic with FeLV-C/Sarma and FeLV-A/61E, marrow FBs and FB cell clones were isolated and assayed for expression of FeLV gag protein. From 30% to 86% and 64% to 88% of marrow FB precursors were infected with FeLV-C/Sarma and FeLV-A/61E, respectively. CFU-F from a cat viremic with FeLV-A/61E were not affected by exposure to antibody against FeLV envelope glycoprotein gp70 and heterologous complement, whereas similarly treated hematopoietic progenitors (erythroid colony-forming units, CFU-E; erythroid burst-forming units, BFU-E; and granulocyte-macrophage colony-forming units, CFU-GM) and culture-propagated, FeLV-infected marrow FBs were effectively lysed, suggesting that infected CFU-F within the marrow microenvironment do not express a significant amount of gp70 on their cell membranes. Thus, marrow FB precursor cells appear to be a major target for FeLV in vivo. Furthermore, the low level of gp70 antigen expression on the surface of these cells in vivo may allow them to escape immune surveillance and provide a reservoir of virus during active or latent infection.
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PMID:In vivo infection of marrow stromal fibroblasts by feline leukemia virus. 132 84

The IgE-dependent activation of mononuclear phagocytic cells through their capacity to express low affinity IgE receptors (Fc epsilon RII) has been proposed as a mechanism for the development of airways inflammation in allergic asthma. This Fc epsilon RII expression leads to the IgE-dependent production of the potent pro-inflammatory cytokines IL-1 beta and TNF-alpha. Expression by monocytes of Fc epsilon RII is regulated by several cytokines including interleukin-4, gamma- and alpha-interferons, and granulocyte-macrophage and macrophage colony stimulating factors. An anti-inflammatory effect of nedocromil on monocytes has been proposed as a possible mechanism for its anti-asthma activity. We therefore investigated the capacity of nedocromil to modulate mononuclear phagocyte Fc epsilon RII expression and cytokine production. We used an anti-Fc epsilon RII antibody and flow cytometric analysis to assess the capacity of nedocromil to modulate cytokine-induced Fc epsilon RII expression in normals and asthmatics. Monocytes, THP-1 monocyte leukaemia cells, and alveolar macrophages were exposed to varying concentrations of these cytokines for 48 hr at 37 degrees C with or without the additional presence of nedocromil (1-10 microM) and the per cent of monocytes expressing Fc epsilon RII was determined. No changes in Fc epsilon RII expression were observed. Subsequently, we investigated the capacity of nedocromil to affect the capacity of IgE plus anti-IgE complexes, allergen, and LPS (16 hr/37 degrees C) to stimulate IL-1 beta and IL-6 production. No changes were observed when nedocromil was applied concomitant with the stimulus.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Anti-inflammatory effects of nedocromil sodium: inhibition of alveolar macrophage function. 133 83

We investigated the expression profiles of lacto-series type 2 antigens in hematopoietic cells and their progenitors, in comparison with leukemic leukocytes. Reactivity profiles of various anti-type 2 chain monoclonal antibodies (MoAbs) with leukemic blasts from 12 patients with acute myeloblastic leukemia (AML) and those from two patients with acute unclassified leukemia (AUL) show that anti-sialosyl-Le(x) MoAb SNH3 reacted strongly with greater than 95% of leukemic blast leukocyte populations from all patients (14 of 14). Another anti-sialosyl-Le(x) MoAb, FH6, showed less reactivity than SNH3 (12 of 14 patients), while anti-Le(y) MoAb AH6 showed reactivity with only 8 of 14 patients. On the other hand, none of the anti-type 2 chain MoAbs reacted with CD34+ normal adult bone marrow (BM) mononuclear cells obtained independently from three healthy volunteers. MoAb SNH3, but not FH6 or AH6, showed complement-mediated cytotoxicity to leukemic blasts from these patients, as well as to myelogenous leukemia cell line HL60. Colony-forming unit granulocyte-macrophage (CFU-GM), but not burst-forming unit-erythroid (BFU-E), was incompletely inhibited by treatment of normal BM mononuclear cells with SNH3 and complement. The absence of type 2 chain antigen expression in hematopoietic progenitor cells and in in vitro hematopoietic colonies (CFU-GM and BFU-E) strongly suggests that application of anti-carbohydrate MoAbs, particularly anti-sialosyl-Le(x) could be useful for elimination of leukemic myeloblasts infiltrating in BM, for purging of leukemic blasts in BM, and for facilitation of autologous BM transplantation.
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PMID:Reactivity profiles of leukemic myeloblasts with monoclonal antibodies directed to sialosyl-Le(x) and other lacto-series type 2 chain antigens:absence of reactivity with normal hematopoietic progenitor cells. 137 Jun 43

We analyzed the maintenance of acute myeloid leukemia clonogenic cells (AML CFU-L) in liquid culture in the presence of five potential differentiation inducers: trans-retinoic acid, 1,25-dihydroxy vitamin D3, interferon gamma, granulocyte colony-stimulating factor (G-CSF), macrophage colony-stimulating factor (M-CSF), used singly and with two combined. The culture medium contained either fetal bovine or human serum from normal donors. CFU-L recovery after 7 days was compared to that observed in control cultures. Of AML cases and HL60 cells, 11/15 displayed greater than 50% CFU-L reduction in response to one or more inducers. In 8/9 responsive cases that underwent the nitroblue tetrazolium (NBT) reduction test, an increase in the percentage of functionally mature (NBT-positive) cells was detected. The combination of retinoic acid with interferon gamma was most effective in reducing CFU-L recovering (8 responsive/15 AML cases), G-CSF and M-CSF displayed either inhibitory or stimulatory activity in different AML cases. The type of serum employed generally did not affect the response to inducers of differentiation. No significant inhibition of the recovery of granulocyte-macrophage colony-forming units was determined by the five inducers in experiments with three normal bone marrow samples. Our experiments indicate that biological differentiation inducers can reduce AML CFU-L self-renewal and increase the proportion of differentiated cells at concentrations that do not affect normal myelopoiesis and could be achieved during treatments in vivo.
Leukemia 1992 Feb
PMID:Self-renewal inhibition of acute myeloid leukemia clonogenic cells by biological inducers of differentiation. 137 69


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