Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0026986 (myelodysplastic syndrome)
 14,926 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

A recombinant human interferon-gamma (IFN-gamma) was added to the clonal and suspension cultures of bone marrow (BM) cells from three patients with refractory anemia with excess of blasts (RAEB) before and after IFN-gamma therapy. IFN-gamma inhibited the hematopoietic progenitor cell growth from normal BM in one patient. In the remaining two patients with RAEB, IFN-gamma at lower concentrations (10-10(2) U/ml) consistently enhanced the growth of hematopoietic progenitors. The addition of IFN-gamma to suspension cultures promoted cellular differentiation in all three cases, as evidenced by persisting cytogenetic changes, Auer-rod containing maturing cells and cytochemical studies. Although IFN-gamma therapy resulted in partial or minor responses, these findings suggest the potential of IFN-gamma to act as an inducer of differentiation in myelodysplastic syndromes both in vitro and in vivo.
 ...
PMID:Interferon gamma induces differentiation of cells from patients with myelodysplastic syndromes in vitro and in vivo. 194 31

The effects of recombinant human interleukin 3 (IL3) on normal bone marrow cells and human leukemic cells were studied. In clonal assays, IL3 supported the growth of all colony types including megakaryocytes. Erythroid colonies were formed in the presence of IL3 and erythropoietin, but not in the absence of erythropoietin. Replating experiments using blast cell colonies derived from a cell population enriched for progenitor cells by fluorescence-activated cell sorting with the monoclonal antibody 3C5, showed that IL3 supported the continued replating of colonies. The clonal proliferation of human bone marrow cells in response to IL3 was inhibited by tumor necrosis factor and by lymphotoxin, but not by interferon-gamma. In suspension cultures, IL3 supported the proliferation of mast cells. Human IL3 had no effect on the growth responses, morphology, cytochemistry, or clonogenicity of the human leukemic cell lines HL60, U-937, KG1a, and HEL. Transcripts for IL3 mRNA were not detectable in these cells, nor in the K562 cell line, implying that autocrine secretion of IL3 was not the mechanism by which these leukemias were maintained. Although cells derived from the bone marrow or peripheral blood of twenty patients with myeloproliferative disorders, myelodysplastic syndromes or acute myeloid leukemia frequently showed proliferative responses to IL3, mRNA transcripts for IL3 were not detected in these cells.
 ...
PMID:Human interleukin 3: effects on normal and leukemic cells. 262 75

T-cell-mediated inhibition of granulomonopoietic progenitors (CFU-GM) was studied in vitro in 27 patients with severe aplastic anaemia (AA). In nine out of 13 responders to anti-thymocyte globulin (ATG), cultured T-cells obtained prior to therapy, as well as their conditioned medium strongly suppressed both normal allogeneic and autologous CFU-GM (the latter obtained after marrow recovery). Addition of anti-interferon-gamma to the cultures abolished the suppressive effect on CFU-GM. After ATG therapy, no similar inhibitory effect was detected. Employing the panning method with monoclonal antibodies (CD4+ for inducer/helper and CD8+ for cytotoxic/suppressor T-cells) we were able to show that the cells responsible for in vitro CFU-GM inhibition were included in the cytotoxic/suppressor T-cell subpopulation. Cultured T-cells and their conditioned medium obtained from 14 non-responders to ATG did not show CFU-GM suppression. The mean interferon (IFN) levels in the T-cell conditioned media of ATG-responders was 625 +/- 125 mu/ml while in non-responders the level was 45 +/- 15 mu/ml (normal control levels 43 +/- 24 mu/ml). Freshly isolated peripheral blood lymphocytes from either group did not show any in vitro inhibitory effect. The response rate to ATG was statistically significant when the generation in culture of high versus low IFN production was compared (P = 0.0001). Experiments with T-cells obtained from heavily transfused thalassaemia major, and myelodysplastic syndrome patients, as well as normal volunteers, also did not demonstrate any suppression of CFU-GM. Our results indicate that the response rate to ATG is significantly higher in patients with AA who have an abnormal regulation of interferon-gamma (g-IFN) production.
 ...
PMID:In vitro interferon-gamma production by cultured T-cells in severe aplastic anaemia: correlation with granulomonopoietic inhibition in patients who respond to anti-thymocyte globulin. 313 95

The effects of interleukin 12 (IL-12) on natural killer (NK) cell cytotoxicity and on the production of interferon-gamma (IFN-gamma) and tumour necrosis factor-alpha (TNF-alpha) were examined in 15 patients with myelodysplastic syndromes (MDS), which are well known to have immunologic defects, and in 11 normal subjects. The NK cell cytotoxicity of all of the normal subjects was augmented by incubation with IL-12 alone, and co-incubation with interleukin 2 (IL-2) further augmented it (type A response). The MDS patients showed varied responses to IL-12/IL-2. Seven patients showed the type A response, resulting in augmented NK cell cytotoxicity which was similar to that in the normal subjects. In five other patients the cytotoxicity was not increased by IL-12 alone, but the combination of IL-12 and IL-2 did augment the cytotoxicity (type B response). The augmented cytotoxicity in these type B patients was lower than that in the normal subjects. In the final three MDS patients the cytotoxicity was low and not affected by IL-12 and/or IL-2 (type C response). All patients with refractory anaemia with excess blasts (RAEB) and patients with RAEB in transformation showed a type B or C response. Conversely, six of eight refractory anaemia patients showed a type A response. In MDS patients there was a positive correlation between the percentage of CD3- CD56+ cells in pre-incubated cells and the cytotoxicity of cells incubated with IL-12/IL-2. The combination of IL-12 and IL-2 augmented IFN-gamma and TNF-alpha production by nonadherent mononuclear cells in a synergistic or cumulative manner, respectively, in most patients. These results suggest that IL-12, alone or with IL-2, may modulate these important immunologic functions in most MDS patients.
 ...
PMID:Effects of interleukin-12 on natural killer cell cytotoxicity and the production of interferon-gamma and tumour necrosis factor-alpha in patients with myelodysplastic syndromes. 778 78

We studied patients relapsing with myeloid leukemias following allogeneic bone marrow transplantation (BMT) for evidence of immune escape by clonal evolution of the leukemia. Relapsed cells from four out of five patients had a reduced ability to stimulate proliferation of lymphocytes from an HLA-mismatched responder. There was decreased susceptibility to lysis by CTL in three and reduced susceptibility to NK-mediated lysis in one. Relapsed leukemias had marked alterations in expression of critical surface molecules involved in immune responsiveness. Three had decreased expression of MHC class I and II, with no change or increase in CD54 (ICAM-1) or CD80 (B7.1). None of these responded to treatment with donor lymphocytes. Three patients showed no change, or increased expression of MHC with no change or decrease in ICAM-1 or B7.1. Two achieved remission - one in response to donor lymphocytes and one following withdrawal of cyclosporine. In one patient transplanted with myelodysplastic syndrome in transformation, interferon-gamma upregulated expression of MHC molecules in relapsed cells and increased their stimulatory capacity and target susceptibility to unmatched responder lymphocytes. These results suggest that immune escape through clonal evolution of the leukemia is a common occurrence in patients who relapse with myelogenous leukemias after BMT.
 ...
PMID:Immune escape from a graft-versus-leukemia effect may play a role in the relapse of myeloid leukemias following allogeneic bone marrow transplantation. 916 43

Bone marrow (BM) hypoplasia is a major cause of death in paroxysmal nocturnal hemoglobinuria (PNH). However, little is known about the molecular events leading to the hypoplasia. Considering the close pathologic association between PNH and aplastic anemia (AA), it is suggested that a similar mechanism operates in the development of their BM failure. Recent reports have indicated apoptosis-mediated BM suppression in AA. It is thus conceivable that apoptosis also operates to cause BM hypoplasia in PNH. If this is the case, PNH clones need to survive apoptosis and show considerable expansion leading to clinical manifestations. We report here that granulocytes obtained from 11 patients with PNH were apparently less susceptible than those from 20 healthy individuals to both spontaneous apoptosis without any ligands and that induced by anti-FAS (CD95) antibody in vitro. The patients' BM CD34+ cells were also resistant to apoptosis induced by treatment with tumor necrosis factor-alpha, interferon-gamma, and subsequently with anti-FAS antibody. In lymphocytes, the pathologic resistance was not discriminated from inherent resistance to apoptosis. Granulocytes from 13 patients with AA and 12 patients with myelodysplastic syndrome (MDS) exhibited similar resistance to apoptosis. CD34+ cells from MDS-BM also showed similar tendency. Thus, the comparative resistance to apoptosis supports the pathogenic implication of apoptosis in marrow injury of PNH and related stem cell disorders.
 ...
PMID:Apoptosis resistance of blood cells from patients with paroxysmal nocturnal hemoglobinuria, aplastic anemia, and myelodysplastic syndrome. 932 38

In patients with paroxysmal nocturnal hemoglobinuria (PNH), we measured plasma concentrations of endogenous hematopoiesis-regulatory cytokines to characterize bone marrow (BM) hypoplasia which is a major cause of death. Contrary to 10 healthy individuals, all 14 patients with PNH showed increases of erythropoietin (Epo) and granulocyte-colony stimulating factor (G-CSF). There were no signs of infection, renal dysfunction or hypoxia. The lower the hemoglobin level and granulocyte count, the higher the plasma Epo and G-CSF levels. In contrast, marked differences were not found in the levels of interleukin-3 (IL-3), tumor necrosis factor-alpha (TNF-alpha), stem cell factor (SCF), granulocyte/macrophage-colony stimulating factor (GM-CSF), or interferon-gamma) (IF-gamma). The cytokine profiles of PNH patients were quite similar to those of patients with aplastic anemia (AA) and myelodysplastic syndrome (MDS). The cytokine profiles may support a pathological relationship between PNH and these stem cell disorders.
 ...
PMID:Markedly high plasma erythropoietin and granulocyte-colony stimulating factor levels in patients with paroxysmal nocturnal hemoglobinuria. 947 72

Gene expression involving apoptosis in the hematopoietic system is reviewed. In normal and hematological disorders, Fas-Fas ligand and tumor necrosis factor-alpha-receptor interaction play a major role in enhancing apoptosis. On the other hand, bcl-2 or certain novel proteins (including FADD, RIP, TRADD and sentrin) prevent apoptosis. Apoptosis is involved in myelodysplastic syndrome and pathogenesis of leukemia. Expression of Fas antigen plays a role in negative regulation of hematopoiesis in the bone marrow as does interferon-gamma.
 ...
PMID:Apoptosis-gene expression in hematopoietic system: normal and pathological conditions (Review). 985 9

Here we show that patients with myelodysplastic syndromes (MDS) have a severe deficiency of glycolipid reactive Valpha24+/Vbeta11+ natural killer T (NKT) cells, but not NK cells or CD4+ or CD8+ T cells. Neither the blood nor marrow of MDS patients had detectable interferon-gamma-producing NKT cells in response to the NKT ligand, alpha-galactosyl ceramide, although influenza-virus-specific effector T-cell function was preserved. This severe and selective deficiency of an important immune regulatory cell may contribute to the pathogenesis of MDS.
 ...
PMID:Severe and selective deficiency of interferon-gamma-producing invariant natural killer T cells in patients with myelodysplastic syndromes. 1289 17

To explore the difference of negative regulatory factors among T lymphocyte subsets in bone marrow (BM) of myelodysplastic syndromes (MDS) and their relations to apoptotic gene Fas, different lymphocyte subsets in BM were categorized by monoclonal antibodies with 3 color fluorescence using flow cytometry, and the intracellular cytokines such as tumor necrosis factor-alpha (TNF-alpha), interferon-gamma (IFN-gamma) were determined following marrow cells culture. Then Fas mRNA of bone marrow mononuclear cells (BMMNC) were examined by RT-PCR. The results showed that TNF-alpha, IFN-gamma levels in BM of MDS both increased, the former produced by cells CD4+CD45RO+, CD8+CD45RO+, the latter by cells CD4+CD45RO+, CD8+CD45RO+, CD8+CD45RA+, in which the cells CD8+CD45RO+ were dominant. Fas mRNA expression had relationship with IFN-gamma produced by T cells but not with TNF-alpha. It is concluded that in hematopoietic microenvironment of MDS, not only the T lymphocyte subsets are in disorder, but also negative regulatory factors secreted by T lymphocyte increase. T lymphocytes play an important role in producing IFN-gamma in patients with MDS.
 ...
PMID:[Study on negative regulatory factors in bone marrow mononuclear cells of myelodysplastic syndromes]. 1549 20


1 2 Next >>