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

Myelodysplasia (MDS) is mostly characterized by a normal or increased number of normoblasts in the bone marrow and an impaired in vitro colony formation. In the present study we analyzed whether this might be due to a disconnection between proliferation and differentiation. CD34+/CD36- sorted bone marrow cells of 18 MDS patients were cultured in a clonogenic and suspension culture assay in the presence of erythropoietin (Epo) and mast cell growth factor (MGF). Burst-forming units erythroid (BFU-E, 75 +/- 88/10(4) CD34+ cells, X +/- s.d.) and colony-forming units E (CFU-E) were observed in eight of the 13 cases (62%) with refractory anemia with or without ring sideroblasts (RA and RARS) and one of the five cases with RA with excess of blasts or in transformation (RAEB and RAEB-T). Suspension cultures with CD34+/CD36- sorted cells with Epo plus MGF demonstrated an 8.9 +/- 6.5-fold expansion after 7 days in cases with >10 BFU-E/10(4) CD34+/CD36- cells while cases with <10 BFU-E/10(4) CD34+/CD36- cells demonstrated 1.0 +/- 0.8-fold expansion especially in cases with RAEB/RAEB-T. FACS and morphology analysis after 7 days of suspension culture demonstrated partial differentiation along the erythroid lineage in cases with RA/RARS (75%) and RAEB/RAEB-T (66%) reflected by the presence of erythroblasts and normoblasts with variable expression of CD34, CD36 and Glycophorin A. In cases with erythroid colony formation 69 +/- 24% of the cells were CD34-/CD36+ and in cases with <10 BFU-E/10(4) CD34+ cells 18 +/- 16% of cells were CD34-/CD36+. Iron staining showed the presence of ring sideroblasts in two cases with RARS indicating that the cells originate from the abnormal erythroid clone. Finally, it was shown that cases with an impaired proliferative response demonstrate an enhanced binding of Annexin-V on CD34+ cells during the first days of the cell suspension culture phase. These results suggest that a defect in the proliferative response is most pronouncedly expressed in MDS whereas a subpopulation of cells retain the capacity to differentiate between transition to a terminated stage.
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PMID:CD34+/CD36- cells from myelodysplasia patients have a limited capacity to proliferate but can differentiate in response to Epo and MGF stimulation. 1008 48

Bone marrow aspirates of 19 patients with low-risk myelodysplastic syndromes (MDS) and 14 control subjects were collected in order to assess the level of oxidative DNA damage. Glycophorin A positive and negative cells separated by miniMACS magnetic cell sorting were subjected to single cell gel electrophoresis (comet assay) combined with enzymes of base excision repair (endonuclease III and formamido-pyrimidine-glycosylase) that specifically recognize oxidized nucleotides. Compared to controls, MDS patients exhibited a significant increase of oxidative damage to DNA which could contribute to genomic instability and disease progression.
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PMID:Oxidative DNA damage in bone marrow cells of patients with low-risk myelodysplastic syndrome. 1868 69

Myelodysplastic syndromes (MDS) are a heterogenous group of stem cell disorders characterized by an impaired differentiation of the pluripotent stem cell resulting in dysplastic changes of all three hemopoietic lineages. We studied the effect of vitamin D (Vit.D) or all-trans retinoic acid (ATRA; 10(-6) and 10(-8)M) in combination with GM-CSF on the proliferation and differentiation of mononuclear bone marrow-cells (MNC) of 48 MDS-patients as compared to 9 normal bone marrow (BM)-controls in a special colony assay: 30,000 MNC were cultured in agar plugs for 7 days (d) and the resulting colonies immunophenotyped in situ by a panel of monoclonal antibodies. In 14 of 48 cultured MDS-BM-samples hemopoietic clones could be grown which expressed myelomonocytic antigens (CD14 (21%*), CD15 (35%*)) as well as blast antigens (CD20 (9%*), CD34 (10%*), Glycophorin A (Glyco A, 18%*)) whereas all normal BM-colonies were negative for blast markers. Vit.D or ATRA in combination with GM-CSF could not induce an (immunologically measurable) increased differentiation (5 higher percentage of differentiated clones) as compared to GM-CSF alone. We conclude that Vit.D and ATRA have no sufficient differentiation effect on MDS-cells. Our colony assay in combination with immunophenotyping enables an in vitro measurement of differentiation and proliferation in MDS. We suggest the use of this technique to measure effects of therapy in the course of the disease.
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PMID:Effect of GM-CSF, 1, 25-Dihydroxycholecalciferol (Vit.D) and All-Trans-Retinoic Acid (ATRA) on the Proliferation and Differentiation of MDS-Bone Marrow (BM)-Cells In Vitro. 2740 22