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)

A 78-year-old man presented with marked thrombocytosis (126.4 x 10(4)/microliters), low neutrophil alkaline phosphatase (NAP) score and an abnormal karyotype of 46, XY, del(20) (q11q13) (18 of 20 cells), without obvious anemia or ringed sideroblasts in bone marrow. He received ranimustine (MCNU) with a diagnosis of essential thrombocythemia. After 2 years, he was admitted because of macrocytic anemia. The peripheral blood smear showed anisopoikilocytosis with a few nucleated red blood cells. Moderate thrombocytosis (71.7 x 10(4)/microliters) and a low NAP score were also observed. Bone marrow aspiration revealed erythroid hyperplasia with a significant increase in ringed sideroblasts (85% of erythroblasts). Cytogenetic studies showed the same abnormal karyotype 46, XY, del(20) (q11q13) in 100% of metaphase cells as those at initial diagnosis. A diagnosis of sideroblastic anemia preceded by essential thrombocythemia was made. No rearrangement or amplification of c-src was revealed. The observation of the same chromosome abnormality (20q-) in different phases of this patient's disease indicates that chronic myeloproliferative disorders and myelodysplastic syndrome may share some borderline or transitional cases with a similar pathogenesis.
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PMID:[Sideroblastic anemia preceded by essential thrombocythemia with 20q- chromosome abnormality]. 823 Jul 46

The aim of the present study was to evaluate the function of granulocytes in 20 patients affected by myelodysplastic syndrome (MDS) and correlate this with the expression of surface membrane integrins. The granulocytes showed a deficit in chemotaxis (34 +/- 12 vs 84 +/- 10, p < 0.01) in superoxide release (12 +/- 7 vs 30 +/- 10, p < 0.01) and in aggregation 12 +/- 6 vs 36 +/- 9, p < 0.01 using fMLP as stimulus. We also demonstrated with cytofluorimetric and alkaline phosphatase immunoenzymatic analysis (APAAP), decreased expression of CD11b/CD18 receptor detected by OKM1 (p < 0.001) and CD18 detected by MoAb IOT-18 (p < 0.001). PMNs CD11b/CD18 up-regulation and APAAP image analysis studies showed a lower level of expression of CD11b/CD18 in granulocytes from MDS patients compared to controls (p < 0.001). We concluded that granulocyte dysfunction in MDS may be correlated with modification of leukocyte integrins.
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PMID:The role of integrins in granulocyte dysfunction in myelodysplastic syndrome. 832 43

A novel long-term cultured interleukin (IL)-3-dependent human myelodysplastic cell line, MDS92, was shown to contain several myeloid-lineage cells such as neutrophils, macrophages, eosinophils, and a small number of megakaryocyte-lineage cells. Therefore this cell line possesses at least bipotential characteristics of myeloid- and megakaryocyte-lineages. Granulocyte colony-stimulating factor clearly promoted the neutrophil alkaline phosphatase activity of MDS92 cells. To the contrary, the incidence and growth of CD41-positive cells were hardly affected by the addition of IL-6, IL-11, c-mpl ligand (thrombopoietin, TPO) or erythropoietin. TPO slightly supported the growth of CD34-positive cell fraction, but not CD41-positive cell fraction of MDS92 cells in combination with IL-3 or Steel factor. This cell line will be a useful tool for the study of MDS stem cells, but the mechanism of commitment of differentiation in MDS stem cells remains unknown.
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PMID:A novel factor-dependent human myelodysplastic cell line, MDS92, contains haemopoietic cells of several lineages. 854 20

The mRNA expression of alkaline phosphatase (ALP), myeloperoxidase (MPO), defensin and G-CSF receptor (G-CSFR) in bone marrow cells of normal individuals and myeloid disorders, with or without in vitro stimulation by myeloid cell growth factors, i.e. G-CSF, GM-CSF and IL-3, were examined as markers for myeloid cell differentiation in both mononuclear cell (MNC) and polymorphonuclear cell (PMN) fractions. Without any stimulation, ALP mRNA was expressed only in PMNs, G-CSFR mRNA in PMNs were expressed stronger than in MNCs; both MPO and defensin mRNA were expressed to the same degree in both fractions. With stimulation, the ALP mRNA expression in both fractions was strongly enhanced by G-CSF, but the expression was inhibited by GM-CSF and/or IL-3. MPO mRNA expression was stimulated by G-CSF and/or GM-CSF in MNCs. G-CSFR mRNA expression was enhanced by G-CSF in both fractions. Defensin mRNA expression was inhibited by G-CSF. In cases of myelodysplastic syndrome and chronic myelogenous leukaemia which display a suppressed maturation of myeloid cells, our results demonstrated an almost normal response to these growth factors. Our results suggest that studies on these myeloid marker mRNA expressions would provide more knowledge about the differentiation state and cytokine reactivity of myeloid cells in normal individuals as well as various disorders.
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PMID:Effects of myeloid cell growth factors on alkaline phosphatase, myeloperoxidase, defensin and granulocyte colony-stimulating factor receptor mRNA expression in haemopoietic cells of normal individuals and myeloid disorders. 856 17

The Fgr protein-tyrosine kinase, p55(c-fgr), is specifically expressed and functions in cells of myelomonocytic lineages. We examined levels of expression and enzymatic activity of p55(c-fgr) peripheral blood neutrophils of patients with myelodysplastic syndromes (MDS) and chronic myelogenous leukemia (CML) by comparison with those of normal individuals. While neutrophils of eight normal subjects gave uniform results, the specific enzymatic activity of p55(c-fgr), a ratio of the total kinase activity versus the protein level was reduced in seven out of eight patients with MDS and all of five patients with CML. The specific kinase activity of p55(c-fgr) correlated significantly with the activity of neutrophil alkaline phosphatase (NAP) which has been considered to be a marker of neutrophil maturity (r=0.568, P<0.01). The reduced activity of this tyrosine kinase was considered to be a biological parameter for immaturity and to reflect dysfunction of neutrophils of patients with MDS and with CML.
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PMID:Activity of Fgr protein-tyrosine kinase is reduced in neutrophils of patients with myelodysplastic syndromes and chronic myelogenous leukemia. 863 16

Trisomy 13, as a sole karyotypic abnormality in acute leukemia, has been reported in several cases. However, in chronic myelogenous leukemia (CML), only two cases with this abnormality were reported so far. We describe herein a 68-year-old case with Philadelphia chromosome-negative CML and trisomy 13. Leukocytosis was pointed out during the treatment for other diseases. After 7 months, abrupt increase in leukocyte count (108,000/microliters) and splenomegaly developed. Decreased neutrophil alkaline phosphatase activity and morphological features fulfilled the diagnostic terms for CML. However, the karyotypic analysis revealed trisomy 13 instead of Philadelphia chromosome, and the BCR gene rearrangement was not detected. In cases with acute leukemia accompanied by trisomy 13, malignant transformation of an immature hematopoietic precursor cell has been suggested by the expression of antigens characteristic of both the myeloid and lymphoid lineage. In a few cases with myelodysplastic syndrome, a multipotent stem cell disorder, trisomy 13 has also been reported. From these standpoints, there might be a possibility that trisomy 13 as a sole abnormality in hematologic disorders would be related to tumorigenesis in the levels of multipotent stem cells.
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PMID:[Philadelphia chromosome-negative chronic myelogenous leukemia with trisomy 13]. 869 71

Serum cholesterol level as well as serum lactate dehydrogenase (LDH), alkaline phosphatase (ALP) and gamma-glutamyl transferase (GGT) were measured in 65 samples of bone marrow blood and in matched peripheral blood taken from patients with various hematological diseases. As expected, serum LDH activities were higher and serum total cholesterol levels were lower in the bone marrow blood than in the blood taken from the cubital vein. More interestingly, an important increase of heat-labile ALP, but not of serum GGT, was found in the bone marrow blood obtained from patients characterized by a proliferating bone marrow. Actually, both LDH and ALP activities were obviously higher in the bone marrow blood of patients with megaloblastic anemia, myelodysplastic syndrome and chronic myeloid leukemia than in samples taken from patients with chronic lymphocytic leukemia, a disease characterized by a slower proliferation rate. While the expected increased LDH activity is the result of an accelerated turnover of bone marrow cells implying the release of this enzyme from the dividing and/or decaying cells, the much higher activity of the heat-labile alkaline phosphatase found in the bone marrow blood would reflect an enhanced local remodeling of bone structures, probably related to an expanded proliferating bone marrow. The lower serum cholesterol level in the bone marrow blood could be subsequent to an enhanced uptake of low density lipoproteins by specific receptors on the bone marrow cells.
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PMID:Serum lactate dehydrogenase and alkaline phosphatase activities and serum cholesterol level in bone marrow blood. 916 17

Thirty-five patients, 24 males and 11 females, with myelodysplastic syndromes were studied for the expression of c-myc encoded p67 oncoprotein. According to FAB classification, 5 patients had refractory anaemia (RA). 5 refractory anaemia with ringed sideroblasts (RARS), 17 refractory anaemia with excess of blasts (RAEB), 4 refractory anaemia with excess of blasts in transformation (RAEB-t), and 4 chronic myelomonocytic leukaemia (CMML). The mouse anti-human 9E10 derived monoclonal antibody in the standard APAAP technique for immunohistochemical analysis was used. A scoring method similar to that routinely used for endogenous neutrophil alkaline phosphatase estimation, was applied to obtain parametrically comparable results. In all but two MDS patients, the observed c-myc oncoprotein score values did not differ statistically from those found in the controls. The values did not correlate with peripheral blood or bone marrow blast cell numbers. In two out of 17 patients with RAEB in whom very high c-myc score values were found, acute non-lymphocytic leukaemia (ANLL) was diagnosed 30 and 45 days later, respectively. Furthermore, we found high c-myc score values in three patients with RAEB and in two patients with RAEB-t during the ANLL phase which was diagnosed six to ten months after the initial study. Our data suggest that c-myc activation may be seen in all cases of MDS in overt ANLL phase, and also in some RAEB patients a few weeks before diagnosis of overt ANLL. The possible prognostic value of c-myc activation in MDS patients remains to be clarified.
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PMID:Increased expression of c-myc p67 oncoprotein in patients with myelodysplastic syndromes in transformation to acute leukaemia. 928 97

Increased susceptibility to infections in patients with myelodysplastic syndromes (MDS) is thought to be due to neutropenia as well as functional abnormalities of neutrophils. In the present study we examined the effect of two different stimulants (fMLP, PMA) and three cytokines (alphaTNF, G-CSF and GM-CSF), both singly and in combination on granulocyte (RB) in 25 MDS patients compared to seven healthy controls. Single fMLP and PMA-stimulation showed similar results for both groups. Preincubation with cytokines enhanced fMLP-stimulated RB in most MDS patients and controls, but in patients to a significantly lesser extent when compared to the control group (p < or = 0,05). Combinations of alphaTNF + GM-CSF and alphaTNF + G-CSF were highly synergistic in priming fMLP-stimulated burst in both groups. But again, as with the single cytokine priming this effect was markedly reduced in MDS patients compared to controls (p < or = 0,05). A specific priming defect for one of the cytokines or a cytokine combination could not be demonstrated. Serum alphaTNF levels were measured in 18 and neutrophil alkaline phosphatase (NAP) index in 23 patients. Results did not correlate with variations of the RB in MDS patients. We conclude that reduced alphaTNF, GM-CSF and G-CSF priming of granulocyte RB is a frequent finding in MDS and may contribute to the enhanced susceptibility to bacterial infections.
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PMID:Cytokine priming of the granulocyte respiratory burst in myelodysplastic syndromes. 937 5

To the significance of basophilia in haematopoietic disorders, six draw attention to cases have been analyzed. Associated diseases included acute myelogenous leukaemia (AML-M2, M3, M4, and M6), refractory anaemia with excess of blasts (RAEB) and RAEB in transformation (RAEB-T). Two AML cases (M2, M6) were preceeded by myelodysplastic syndromes (MDS). All patients showed greater than 3% basophilia in peripheral blood and bone marrow. Basophils were identified successfully by metachromatic staining with toluidine blue in all cases. Three patients (M3, M4, RAEB) presented with lymphadenopathy, suggesting an association with extramedullary involvement. Neutrophil alkaline phosphatase (NAP) activity was significantly reduced in four patients with AML (M2, M3, M4) and RAEB-T. The clinical course was generally unfavourable characterized by short remission duration or disease progression except for the patient with RAEB. Haemorrhage was the main cause of death rather than infection. Cytogenetic analysis revealed unique abnormalities involving chromosomes 3q21, 5q31, and 17q11 where the genes for some haematopoietic growth factors or their receptors are located, in addition to t(6;9) and t(15;17).
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PMID:Importance of basophilia in haematopoietic disorders. 1006 49


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