Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0002874 (aplastic anemia)
 5,905 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We have recently shown that in patients with aplastic anemia (AA) recovering following immunosuppressive therapy, the persistent reduction in the bone marrow clonogenic potential is unrelated to suppressive effects of the myeloid stroma and intrinsic to the hematopoietic progenitors. We examined the mechanisms of this defect by determining the response of the aplastic CD34+ clonogenic precursors to proliferative signals induced by hematopoietic growth factors and comparing their results with those of a control population. Light density bone marrow mononuclear cells were lymphocyte and monocyte depleted and enhanced for the CD34+ progenitors by immunomagnetic selection. Selected progenitors were then cultured in the mixed colony assay with incremental concentrations of combinations containing erythropoietin (Epo), granulocyte-macrophage colony-stimulating factor (GM-CSF), interleukin-3 (IL-3) and c-kit ligand. Bone marrow from aplastic patients had significantly fewer light density cells displaying the CD34 antigen (mean 0.65%, SD 0.35 vs. 1.62%, SD 1.4; p=0.002). Dose response studies on aplastic CD34+ cells demonstrated that at low concentrations of Epo, IL-3 and GM-CSF, clonogenic growth was significantly impaired but achieved normal values at concentrations giving plateau growth in control cultures. However, for all colony types, responses to effective concentrations of c-kit ligand corresponded with those of controls. These data suggest abnormalities at the receptor or signal transduction levels.
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PMID:In aplastic anemia progenitor cells have a reduced sensitivity to the effects of growth factors. 1048 68

Appropriate adhesion between bone marrow stem cells and the marrow microenvironment is necessary for hematopoiesis, since signals that promote maturation or apoptosis are transmitted from stromal cells to stem cells. In aplastic anemia (AA), interferon-gamma produced by stromal cells has more influence on the pathogenesis of marrow failure than interferon-gamma produced by lymphocytes. We evaluated the expression of cell adhesion molecules, such as very late antigen-4 (CD49d), and -5 (CD49e) or c-kit receptor (CD117), by CD34-positive bone marrow cells in patients with AA who achieved hematological complete remission after immunosuppressive therapy. Before treatment, CD34-positive cells showed markedly higher expression of CD49d and CD49e than cells from healthy controls, indicating the strong adhesion of stem cells to the bone marrow stroma. Expression of CD49d and CD49e was significantly decreased, reaching normal levels, after hematological recovery. These findings suggest that changes in adhesion molecule expression by stem cells are important in the pathology of AA.
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PMID:Adhesion molecule expression by bone marrow CD34-positive cells in aplastic anemia before and after immunosuppressive therapy. 1464 Nov 44

In order to investigate the levels of stem cell factor (SCF) and its receptor c-kit protein and mRNA in pediatric aplastic anemia (AA) and their relevance to the pathogenesis, immunocytochemical and in situ hybridization were utilized to detect the expression of SCF and its receptor c-kit gene protein and mRNA, respectively in 59 children with AA and 51 normal controls. The relationship between SCF and c-kit and the pathogenesis of AA was analyzed subsequently. The results showed that the positive rate of SCF protein and mRNA expression in children with AA was significantly lower than that in healthy controls (P < 0.05). However, there was no significant difference in the positive rate of c-kit protein and mRNA expression between children with AA and control group (P > 0.05). It was concluded that the expression of SCF is significantly decreased in children with AA, which may be closely associated with the pathogenesis of the AA. c-kit may be unrelated to the development of pediatric AA. Therefore, AA in children may have abnormalities at SCF/c-kit signal transduction levels.
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PMID:Role of stem cell factor and its receptor in the pathogenesis of pediatric aplastic anemia. 1593 1

The production of blood cells from bone marrow (BM) hematopoietic stem cells (HSC) is regulated by a number of cytokines and growth factors that influence cell survival; differentiation, proliferation and apoptosis in health and supposedly, such mechanisms are deregulated in diseased conditions. As far as cellular kinetics is concerned HSCs are relatively quiescent in adults, have the ability to replicate symmetrically and asymmetrically and predictably exhibit multi-lineage hematopoietic reconstitution potential. HSC drive hematopoiesis and homeostasis by contracting and expanding the pool of hematopoietic cells in the bone marrow. In mouse they can be identified immunophenotypically as Sca1+ c-kit cells. In aplastic anemia a drastic decline in the marrow efficacy to produce mature blood cells leads to bone marrow failure. In contrast, in leukemia hyper stimulated marrow leads to deregulated differentiation of immature hematopoietic stem cells with increased self-proliferation potential. In our experimental set up, we induced aplastic anemia by injecting busulfan and cyclophosphamide and leukemia by N-N' ethylnitrosourea intraperitoneally in inbred swiss albino mice. Indeed, HSCs and haematopoietic progenitor cells (HPCs) are vulnerable target for such disease oriented dysregulation which bears close correlation with the bone marrow microenvironmental damage. The present study aims at evaluating the possible mechanism(s) of deregulation in the bone marrow physiology with special reference to HSC surface receptor expression, cellular granularity, cell cycle status and overall marrow architecture. The investigations made so far revealed an interesting correlation between disease initiation and specific cytokinetic involvement of HSC in the BM microenvironment with particular reference to leukemia and aplastic anemia.
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PMID:Kinetic impairment of haemopoietic stem cells in experimentally induced leukemia and aplastic anemia: an inverse correlation. 2023 2


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