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Query: UMLS:C0026986 (myelodysplastic syndrome)
 14,926 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Conflicting results have been published on whether or not myelodysplastic syndromes (MDS) affect all cell lineages. Involvement of myeloid and erythroid cell lineages has been regularly observed, but it remains controversial whether the different lymphoid cell lineages are involved. In this study of eight patients with MDS associated with monosomy 7, fluorescent in situ hybridization (FISH) was used to enumerate the chromosomes 7 in interphase cells. With the probe D7Z1, the rate of false-positive detection of monosomy 7 was 3% +/- 2% in normal cells. T- and B-cell lines were established from eight patients with MDS and monosomy 7. As determined by FISH in interphase cells, 1.9% (0% to 3%) of the cells in the B-cell lines showed one fluorescent spot and 1.1% (0% to 2.9%) of the cells in the T-cell lines. These values do not differ from normal values. However, the possibility that normal cells were selected when the T- and B-cell lines were established could not be excluded. Therefore, peripheral blood cells were obtained, separated according to surface markers specific for lymphoid and myeloid cell lineage with a cell sorter, and analyzed for the expression of monosomy 7 by FISH. Antibodies recognizing T cells (CD3), B cells (CD20), natural killer (NK) cells (CD57), monocytes and granulocytes (low and high expression of CD11b antigen), and myeloid progenitors (CD33) were used to separate cells. The expression of monosomy 7 in the T cells, NK cells, and B cells did not differ from control values. These results in the lymphoid subpopulations are in stark contrast with the observations in the myeloid populations; the percentage of cells with monosomy 7 ranged from 9% to 78% (controls: 6% +/- 2%) in cells with low CD11b expression, 20% to 89% in cells with a high expression of the CD11b antigen (controls: 7% +/- 3%), and 23% to 91% in the CD33 positive cells (controls: 5% +/- 3%). The results of this study suggest that monosomy 7 does not usually affect lymphoid subpopulations but is restricted to committed progenitor cells with the capacity to differentiate into mature myeloid cells.
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PMID:Clonal analysis of myelodysplastic syndrome: monosomy 7 is expressed in the myeloid lineage, but not in the lymphoid lineage as detected by fluorescent in situ hybridization. 161 Oct 87

A five-year-old boy initially diagnosed common ALL was developed to acute myelomonocytic leukemia. At onset, the bone marrow was hypercellular and 77% of the cells were blasts, mainly lymphoblast-like cells and cytogenetic study demonstrated 45, XY, -7 in all blasts. Cytochemically most of those blasts were negative for peroxidase, sudan black B, alpha-NB esterase staining. The immunological phenotype was J5 (CD10)+, I2 (HLA-DR)+, SmIg-, CyIgmu-, Leu1 (CD5)-, OKT11 (CD2)-, MY7 (CD13)-, suggesting common ALL. Eight months later, the bone marrow cells were occupied with large sized blasts which were almost positive for peroxidase stain and the cells showed coexpression of Mo1 (CD11b)+, MY4 (CD14)+, MY7+, MY9 (CD33)+, MCS2 (CD13)+, I2+, J5-, B4 (CD19)-, Mo2 (CDw14)-, at relapse. He died 2 years and 6 months after his initial diagnosis. An autopsy was performed which revealed generalized infiltration of leukemic cells and aspergillosis of the lung. In general, monosomy 7 is associated with myelodysplastic syndrome in childhood, and is terminated to acute myeloblastic leukemia. In this case, bone marrow blasts demonstrated monosomy 7 cytogenetically, and this case was considered as an acute mixed lineage leukemia of bilineal type. And this case proved that a monosomy 7 can also be terminated to acute mixed lineage leukemia with both lymphoid and myeloid phenotypes.
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PMID:[An autopsy case of acute mixed lineage leukemia with monosomy 7 in a child]. 194 26

We studied the long-term in vivo effects of recombinant granulocyte-macrophage colony stimulating factor (rhGM-CSF) on granulocyte functions in nine patients with myelodysplastic syndrome (MDS). The treatment schedule consisted of a 14 d course of rhGM-CSF (250 micrograms/m2/d s.c.) for patients with refractory anaemia (RA) and refractory anaemia with ringed sideroblasts (RARS), while patients with refractory anaemia with excess of blasts (RAEB) and refractory anaemia with excess blasts in transformation (RAEBt) received a 14 d combination course of rhGM-CSF (250 micrograms/m2 s.c.) and low dose cytosine arabinoside (20 mg/m2 s.c.). rhGM-CSF increased the mean neutrophil count from 3.9 x 10(9)/l to 44 x 10(9)/l. Significant increases of myeloperoxidase content in granulocytes occurred during treatment (P = 0.003). Phagocytosis and killing of Staph. aureus by granulocytes was markedly enhanced during treatment. Microbicidal capacity normalized in four out of six patients during GM-CSF therapy. However, chemotaxis in response to zymosan-activated serum (ZAS) and f-Met-Leu-Phe (f-MLP), was further impaired on the last day of treatment, which was associated with a marked increase in the expression of the granulocyte adhesion receptors CD11a (P = 0.01), CD11b (P = 0.002), CD11c (P = 0.00015) and CD18 (P = 0.0014). GM-CSF therapy did not cause significant changes in hexose monophosphate (HMP)-shunt activity, chemiluminescence, nor superoxide production. The present results show that in vivo administration of GM-CSF is able to repair at least in part the neutrophil anomalies in patients with myelodysplastic syndrome (MDS), which might be useful in modulating host response to infections. However, increased adherence and impaired chemotaxis may explain some toxicities observed during treatment with GM-CSF.
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PMID:In vivo administration of granulocyte-macrophage colony stimulating factor enhances neutrophil function in patients with myelodysplastic syndromes. 195 74

Autonomous, factor-independent growth and differentiation of malignant cells in preleukemic and leukemic disease states is a well-recognized phenomenon and is often associated with a poor prognosis. Mast cells are distinct hematopoietic cells and express a unique profile of antigens. Growth and differentiation of normal mast cells is dependent on mast cell growth factor (MGF), the ligand of the c-kit protooncogene product. In this study, we screened for mast cell-lineage involvement in 52 patients suffering from myeloid leukemias, myelodysplastic syndromes (MDS), systemic mastocytosis, or other diseases by probing for mast cell-related molecules (c-kit, tryptase, histamine, and MGF) and by analyzing kit ligand/MGF-independent growth of mast cells in long-term suspension culture. Of the 52 patients tested, 2 patients with refractory anemia with excess of blast cells in transformation and 1 patient suffering from chronic myeloid leukemia blast crisis (CML-BC) were diagnosed as mastocytic disease. These patients were characterized by complex chromosomal abnormalities, splenomegaly, high percentages of circulating metachromatic cells (5% to 25%), high levels of cellular tryptase (> 10 ng/10(5) peripheral blood mononuclear cells/mL) and a tryptase/histamine (ng:ng) ratio greater than 1. The metachromatic cells expressed the mast-cell-related surface antigen c-kit, but not basophil-related antigens (CD11b, CDw17). Furthermore, in these 3 patients, spontaneous, MGF-independent growth of mast cells along with spontaneous synthesis of tryptase was demonstrable in long-term culture. No autocrine production, paracrine production, or overproduction of MGF was found. The spontaneous growth of mast cells could neither be abbrogated by addition of monoclonal antibodies (MoAbs) to c-kit nor by MoAbs against MGF (< 5% inhibition), whereas factor (MGF)-dependent differentiation of mast cells in these patients could be abbrogated by MoAbs to c-kit or MoAbs to MGF (> 70% inhibition, P < .001). In addition, serum MGF levels in these patients were within the normal range and MGF could not be detected in cell-free culture supernatants. All 3 patients showed rapid progression of disease and had a survival time of less than 1 year. In conclusion, we describe a unique form of transformation in MDS and CML-BC characterized by mast cell lineage involvement and factor-independent differentiation of mast cells. This form of leukemic transformation has to be delineated from chronic myeloid leukemia with basophilia or basophil crisis, from primary mast cell leukemia, and from monocytic leukemias and myelodysplastic disorders associated with basophilia.
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PMID:Kit ligand/mast cell growth factor-independent differentiation of mast cells in myelodysplasia and chronic myeloid leukemic blast crisis. 752 72

We have reviewed the clinical, morphologic, immunophenotypic, and cytogenetic features of 52 patients with erythroleukemia (FAB Cooperative Group; AML-M6) studied by the Cancer and Leukemia Group B (CALGB). The purpose of this study was to correlate morphology with the clinical features, immunophenotypes, and karyotypes of neoplastic cells, and with the response to therapy of patients with AML-M6. Thirty-three patients (63%) were male, median age 59 (range 16-81) years, 47 patients (90%) were white, and 42 patients (81%) had a performance status of < 2. Myelodysplastic changes were observed in at least 1 cell lineage in all cases, and in 2 cell lineages in 45 of 52 (86%) cases. Fifty percent or more of cases studied were positive for CD11b, CD13, CD15, CD33, glycophorin-A, and HLA-DR markers. Fourteen of 27 cases (52%) in whom karyotypic analyses were conducted had cytogenetic abnormalities. Five (19%) were simple (< 3 karyotypic abnormalities), while 9 (33%) were complex (> or = 3 abnormalities). We observed either a complete or partial loss of chromosomes 5, 7, or 12p, or the presence of trisomy 8, in 11 of 27 (41%) patients. Cases of AML-M6 were divided into group 1 (14 patients with bone marrow proerythroblasts and basophilic erythroblasts > 25% of all erythroblasts) and group 2 (38 patients with proerythroblasts and basophilic erythroblasts < or = 25% of all erythroblasts). We observed no significant differences between groups 1 and 2 in regard to sex, age, race, performance status, percentage of blood erythroblasts or myeloblasts, percentage of bone marrow erythroblasts, and periodic acid-Schiff (PAS) or myelodysplasia scores. Six of 6 (100%) patients of group 1, and 7 of 21 (33%) patients of group 2, had normal karyotypes (P = .006). Nine of 13 (69%) patients of group 1 and 15 of 33 (45%) patients of group 2 had a complete remission (CR) (P = .2). Eight of 11 (73%) cytogenetically normal patients achieved CR: 5 of 6 (83%) in group 1, and 3 of 5 (60%) in group 2. Five of 12 (42%) cytogenetically abnormal patients achieved CR. No difference in duration of survival (group 1, median = 4.6 months vs. group 2, median = 10.2 months; P = .93) was observed between the 2 groups. We conclude that AML-M6 is typified by multilineage involvement of hematopoietic cells. The morphology of erythroblasts in patients with AML-M6 may correlate with cytogenetic abnormalities and rate of CR.
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PMID:Morphologic characteristics of erythroleukemia (acute myeloid leukemia; FAB-M6): a CALGB study. 774 Nov 35

We have evaluated the function of granulocytes in 14 patients suffering from myelodysplastic syndrome (MDS). We also evaluated the functional and immunochemical activities of five monoclonal antibodies (MoAbs) reactive with the CD11/CD18 leucocyte adhesion molecules of granulocytes. Granulocytes showed a decrease in chemotaxis (P < 0.001) and in aggregation (P < 0.01) using various agents as a stimulus. Cytofluorimetric and immunoenzymatic assays with alkaline phosphatase (APAAP) analysis showed decreased expression of the CD11b/CD18 receptor detected by OKM1 (P < 0.001). Despite LFA-1 and-CD11a/CD18 was expressed in normal amounts. The studies of upregulation of granulocytes CD11b/CD18 and image analysis of immunochemical preparation (APAAP) demonstrated decreased expression of CD11b/CD18 in granulocytes from MDS compared to controls (P < 0.001). We conclude that granulocyte dysfunction in MDS may be correlated with decreased expression of surface CD11b/CD18 leucocyte adhesion molecules or their structural modification.
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PMID:The CD11/CD18 granulocyte adhesion molecules in myelodysplastic syndromes. 809 50

Infections, an important determining factor in the clinical course of myelodysplastic syndromes (MDS), result in activation of myelomonocytic cells. In this study we demonstrate activation-associated immunophenotypic changes of cell surface antigens on monocytes and granulocytes observed in two groups of MDS patients, one with low and another one with high clinical risk, and compared them to healthy individuals. Significantly changed expression of the complement receptors 1 (CD35) and 3 (CD11b), the Fc gamma receptor I (CD64), the leucocyte-homing receptor (CD44) and the activation associated membrane proteins CD67 and M5 were found on monocytes and/or granulocytes of MDS patients. In low-risk MDS patients we observed activation-associated phenotypic changes only in monocytes, whereas in high-risk MDS patients, both monocytes and granulocytes showed such changes. Additionally, we performed respiratory burst experiments and observed an impaired response of monocytes and granulocytes derived from MDS patients. Despite the fact that all patients were free of infection by clinical criteria, cell surface phenotyping as well as the reduced respiratory burst capacity of myelomonocytic cells suggests in vivo preactivation of these cells.
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PMID:Immunophenotypic characterization of myelomonocytic cells in patients with myelodysplastic syndrome. 810 71

The aim of the present study was to evaluate some functions of neutrophil granulocytes (PMNs), such as aggregation, superoxide production, chemotaxis and adhesion molecules involved in these processes, in 22 patients suffering from Myelodysplastic Syndrome (MDS), to clarify if granulocytes alterations described in this syndrome is really correlated with the expression of surface membrane integrins. Several patients suffering from MDS present granulocytopenia and/or absolute monocytoses; neutrophil granulocytes can have typical nuclear and cytoplasmatic alterations. These granulocytic anomalies are valuable in about 90% of patients suffering from MDS. The granulocytes showed a significant deficit in chemotaxis stimulated by serum activated with E. Coli, casein and formyl-methionyl-leucylphenylalanine (fMLP) (p < 0.01) and in superoxide production stimulated by phorbol-myristate-acetate (PMA). We also studied the role of membrane integrin CD11/CD18 using specific monoclonal antibodies (MoAb). The cytofluorimetric analysis demonstrated a significant inhibition in expression of CD11b/CD18 receptors in patients suffering from MDS (p < 0.001), while the expression of CD11a/CD18 and CD11c/CD18 receptors was normal. In conclusion we found specific alterations in PMNs functions in MDS and a correlation of these anomalies with membrane integrins of PMNs is therefore possible.
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PMID:[Correlations between membrane integrins and granulocyte defects in myelodysplastic syndromes]. 829 Jul 85

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

The FAB classification of myelodysplastic syndromes (MDS) has been useful in predicting prognosis; however, additional methods are required to detect patients at high risk for early conversion to acute nonlymphoblastic leukemia (ANLL). Using a panel of monoclonal antibodies to myelomonocytic surface antigens (MMSA) and flow cytometry, we studied bone marrow cells from 26 patients with MDS of all five FAB subtypes. The MMSA studied included Ia (HLA-DR), CD11b (Mo1), CD14 (Mo2, My4), CD13 (My7), and CD33 (My9). Marrows were considered "positive" for a given MMSA if the percentage of reactive cells exceeded the upper limit of the normal range. Twenty-four of twenty-six patients (92.3%) were CD13 (My7)+, suggesting that CD13 may serve as a diagnostic marker for MDS. Ten of twelve patients who developed ANLL during a median follow-up of 44 weeks were Ia(HLA-DR)+. The Kaplan-Meier estimated median time to leukemia (TTL) was 16 weeks for Ia+ patients and 88 weeks for Ia- patients (P = 0.004). All six patients who developed ANLL before 16 weeks from diagnosis were Ia+, while none of the Ia- patients converted to ANLL before 24 weeks. Nine of thirteen patients with low CD11b (Mo1) expression (< 53% reactive cells) developed ANLL, compared with only two of 11 patients with high CD11b expression (> 53% reactive cells). Kaplan-Meier estimated TTL was 29 weeks for patients with low CD11b, compared to 160 weeks for patients with high CD11b (P < 0.05). Patients who met both criteria, Ia+ and low CD11b, represented the poorest prognostic subgroup, with median TTL of 13 weeks compared with 88 weeks for the others (P = 0.017). Ia and CD11b patterns were not specific for MDS subtype, and their expression did not correlate with blast count. These data suggest that MDS patients whose bone marrow cells demonstrate high Ia (HLA-DR) and low CD11b (Mo1) expression represent a poor prognostic subgroup with short TTL. These patients may be candidates for early aggressive or investigational treatment.
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PMID:High Ia (HLA-DR) and low CD11b (Mo1) expression may predict early conversion to leukemia in myelodysplastic syndromes. 835 30


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