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

The aim of the present study was to evaluate the significance of immunomorphometric assessment of megakaryocyte size and number in normal and pathologic human bone marrow. Thus, we compared morphometric characteristics of megakaryocytes in 56 bone marrow trephine biopsies stained by immunohistochemical and conventional techniques. Morphometric results showed that precise megakaryocyte size in normal and pathologic samples can be calculated even by using conventional staining technique, but only employing specific stereological corrections. Immunomorphometric evaluation revealed populations of "small" megakaryocytes (< 14 microns), "morphologically unrecognized" by conventional staining technique (promegakaryoblasts in normal and stimulated as well as micromegakaryocytes in pathologic bone marrow). In patients with normal and stimulated megakaryocytopoises percentage of "small" megakaryocytes was generally low (10.6% and 14%, respect.); so, megakaryocyte number was similar in immunohistochemically and conventionally stained sections. In contrast, percentages of "small" megakaryocytes were significantly higher in patients with stem cell disorders (namely, myelodisplastic syndrome and chronic granulocytic leukaemia), as compared to controls (35.3% in MDS; 22.9% in CML and 10.6% in controls). In those patients megakaryocyte numbers were more sensitively detected by immunohistochemistry than by conventional staining.
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PMID:[Importance of immunomorphometric evaluation of the size and number of megakaryocytes in normal and pathologic bone marrow]. 771 37

In Down syndrome, acute megakaryoblastic leukemia (AMKL) occurs frequently during the first 4 years of life and is usually preceded by a period of myelodysplasia (MDS), often associated with chromosomal abnormalities. Archival peripheral blood and/or bone marrow films of six patients with Down syndrome and MDS whose leukemic cells contained monosomy 7 or trisomy 8 were studied to determine whether the abnormal precursors produce mature cells in vivo. Using fluorescence in situ hybridization (FISH) of interphase nuclei with chromosome-specific centromere probes for either chromosome 7 or 8, we were able to determine which cells had one, two, or three signals indicative of one, two, or three no. 7 or 8 chromosomes. In five patients with trisomy 8, 80% to 100% (94.5% +/- 6.2%) of the megakaryoblasts had three signals using a chromosome 8 probe; in one patient with monosomy 7, 96.5% of the megakaryoblasts had one signal using a chromosome 7 probe. In all six patients, the myeloid and lymphoid series did not have evidence of the chromosomal abnormality present in the blasts. In three of five patients with trisomy 8, three signals were observed in 27%, 33%, and 41% of normoblasts, respectively. These data are evidence that the abnormal cell in MDS is a progenitor cell with the potential of forming cells of megakaryocyte and erythroid lineages.
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PMID:Interphase cytogenetic analysis of in vivo differentiation in the myelodysplasia of Down syndrome. 791 46

Naked megakaryocyte nuclei (NMN) were studied retrospectively in 100 bone marrow biopsy sections and aspirates from patients with acquired immunodeficiency syndrome (AIDS) and 124 non-AIDS controls. An NMN score was developed to semiquantitate the NMN. The AIDS bone marrows had an incidence of 97% and a mean NMN score of 2.24 which was a higher incidence and score than the control groups and was statistically significant. The control groups consisted of 20 chronic myeloproliferative disorders (incidence of 70% and score of 1.4); 24 cases of acute myelogenous leukemia and myelodysplastic syndrome (incidence of 29.2% and 0.46 score); 22 cases of non-AIDS immune thrombocytopenic purpura (incidence of 50% and 0.82 score); 11 cases of acute lymphocytic leukemia (0% incidence); 21 cases of anemia (52.4% incidence and 0.7 score); and 26 cases of lymphoma staging (35% incidence and 0.35 score). It is concluded that NMN are a very frequent and, with a high score, a specific finding in AIDS bone marrow examinations.
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PMID:Naked megakaryocyte nuclei in bone marrows of patients with acquired immunodeficiency syndrome: a somewhat specific finding. 800 37

An inversion in the long arm of chromosome 3--inv(3)(q21q26)--or a translocation between both homologous chromosomes 3--t(3;3)(q21;q26)--is found specifically in myeloid neoplasias characterized by disturbances of thrombopoiesis and megakaryocyte development. Cytogenetic findings were correlated with clinical and hematological data in altogether 18 patients with acute nonlymphocytic leukemia (ANLL) and with inv(3) (13 patients) or t(3;3) (five patients), six of whom were male and 12 who were female. Chromosomal changes in addition to the 3q anomalies were demonstrated in 14 out of 18 patients, predominantly numerical and structural aberrations of chromosome 7 (12 cases) and/or abnormalities of 5q (five cases). Complex karyotype abnormalities were observed in six of 13 patients with inv(3), but in only one of five patients with t(3;3). In ten out of our 18 patients a preceding myelodysplastic syndrome (MDS) and/or exposure to mutagenic/carcinogenic agents had been established. In eight patients the morphology of ANLL blasts was immature (FAB subtype M1); in three patients ANLL-M4, and in two patients each ANLL-M5, M6, and M7 was diagnosed; in one patient with antecedent MDS the leukemic blasts were not classifiable according to the FAB criteria. A disturbed megakaryocyte development, characterized by an excess of micromegakaryocytes was observed in 14 patients, seven of them showed normal or elevated platelet counts as an unusual feature in patients with ANLL. The clinical course and outcome was extremely poor: 15 of 18 patients died within 10 months after the diagnosis of ANLL. Because of their missing response to conventional chemotherapy, patients with inv(3) or t(3;3) have to be estimated as at high risk. The characterization of genes affected by inv(3) or t(3;3) could help to elucidate molecular changes leading to impaired proliferation and differentiation of hematopoietic cells, also of the megakaryocytic lineage. Based on molecular genetic findings new therapeutical approaches could be designed.
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PMID:Correlation of cytogenetic findings with clinical features in 18 patients with inv(3)(q21q26) or t(3;3)(q21;q26). 805 67

Granulocyte, macrophage colony stimulating factor (GM-CSF) and granulocyte--colony--stimulating factor (G-CSF) are two of the growing number of recognized cytokines involved in the regulation of hematopoiesis. The purification of these factors and the subsequent cloning of the DNAs which encode these proteins have led to their widespread clinical use in the setting up of therapy of disease-induced myelosuppression. GM-CSF has a broader spectrum of potential targets than G-CSF and promotes growth of progenitors of several myeloid lines and, to a lesser extent, of the megakaryocyte line. The pleiotropic effects of GM-CSF could therefore, theoretically, be an advantage compared with the more restricted activity of G-CSF. Its greatest potential use appears to be in the amelioration of neutropenia following myelosuppressive therapy. GM-CSF has demonstrated efficacy in decreasing the duration of neutropenia, decreasing the attendant infection, and enhancing the ability to deliver full doses of myelosuppressive therapy. GM-CSF can also reverse the neutropenia of myelodysplastic syndrome and aplastic anemia. It enhances recovery from bone marrow transplantation and thus reduce the attendant morbidity of this procedure. This hematopoietic growth factor may also enhance recruitment and harvest to peripheral stem cells. At clinically usefull dosages GM-CSF is generally well tolerated.
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PMID:[Biology and clinical applications of GM-CSF]. 806 93

An immunohistochemical and morphometric analysis was performed on bone marrow trephine biopsies in 40 patients with primary myelodysplastic syndromes (MDS) to evaluate the proliferative activity in erythropoiesis and the endoreduplicative capacity of megakaryocytes. Control groups included normal bone marrow and marrow from cases presenting with pernicious anaemia. Double-immunostaining was applied with a monoclonal antibody (PC10) directed against proliferating cell nuclear antigen (PCNA), followed by antibodies against glycophorin C (Ret40f) or platelet glycoprotein IIIa (Y2/51-CD61) for the identification of the erythroid and megakaryocytic cell lineage. Comparison with normal bone marrow showed a reduction of erythropoiesis accompanied by an increase in atypical (micro-) megakaryocytes. Erythroid precursors displayed significant enhancement of PCNA-immunostaining. Megakaryocytes showed no increase in the relative frequency of PC10-positive cells (PCNA-labelling index). In pernicious anaemia, predominance of macrocytic-megaloblastoid erythropoiesis was associated with a striking increase in PCNA-labelling. Cell kinetic studies in this disorder revealed an abnormal arrest, particularly in S-phase which generates an over-expression of PCNA. Similar conditions were believed to be present in MDS with secondary folate deficiency. This mechanism explains the relatively high rate of positively-reacting pro- and erythroblasts which is not invariably accompanied by an increase in cell proliferation. Determination of megakaryocyte size and PCNA-staining capacity resulted in a significant increase in PC10-positive cells among micromegakaryocytes. Our findings on this cell lineage are in keeping with the assumption of a block in endoreduplicative activity at higher ploidy levels, associated with an apparently not-deregulated endomitosis in small-sized megakaryocytes of lower ploidy stages.
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PMID:Myelodysplastic syndromes: immunohistochemical and morphometric evaluation of proliferative activity in erythropoiesis and endoreduplicative capacity of megakaryocytes. 810 4

In vitro colony-forming abilities of highly purified primitive hematopoietic cells in eight cases of myelodysplastic syndrome (MDS) were studied using the blast cell colony assay. Blast cell colony formation from seven normal bone marrow (NBM) samples was studied in parallel. Blast cell colonies were formed in 7/8 cases of MDS, the numbers not significantly differing from those generated by NBM. In contrast the more mature hematopoietic progenitors (granulocyte-erythroid-macrophage-megakaryocyte colony-forming unit, CFU-GEMM; erythroid burst-forming units, BFU-E; granulocyte colony-forming units, CFU-G; eosinophilic colony-forming units, CFU-Eo) were severely depressed in numbers in MDS marrow. After replating of blast cell colonies in secondary cultures, colonies were obtained in 5/8 MDS cases. A marked difference was evident in the composition of the secondary colonies between MDS and normal marrow. Whereas secondary colonies derived from normal blast cell colonies consisted of about 45% of erythroid cells, MDS blast colonies generated mainly colonies of the granulocytic-monocytic lineage and no erythroid colonies. The normal quantitative level of CFU-blast progenitors in MDS in the context of their impaired ability to generate lineage specific progeny upon secondary plating suggests that the incompetence of maturation of MDS may reside in the CFU-blast progenitor cell being incapable of properly responding to growth factor stimulation.
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PMID:Blast colony-forming cells in myelodysplastic syndrome: decreased potential to generate erythroid precursors. 841 82

Bone marrow biopsy (BMB) has aroused growing interest as a possible aid in the diagnostic and prognostic evaluation of myelodysplastic syndromes (MDS). Previous reports have pointed out that MDS patients with blastic aggregates or severe bone marrow (BM) fibrosis are characterized by a worse clinical outcome. BMBs of 106 MDS patients were retrospectively reviewed, and relationships among the different histological parameters as well as clinicopathological correlations were looked for. Three patterns of BM blastic infiltration ("diffuse," "cluster," and "large") were recognized. Overt leukemic transformation and overall survival were selected as prognostic end points. BM infiltration was "diffuse" in 18, "cluster" in 48, and "large" in 40 cases. RAEB-t patients accounted for about half of the "large" cases, and none had a "diffuse" pattern (p < 0.01). Nineteen patients showed extensive BM fibrosis; most of them were characterized by "cluster" blastic infiltration and megakaryocyte hyperplasia. Leukemic transformation occurred in 67% of "large" cases (p< 0.001) and in none of the "cluster" cases with severe BM fibrosis (p < 0.01); however, survival was equally poor in these two groups because of early leukemic transformation (large cases) and BM failure (cluster cases). The FAB classification did not significantly correlate with prognosis. Patients with "cluster" BM infiltration and severe fibrosis can be regarded as a true separate MDS subset characterized by unique clinicopathological and prognostic features. Because of the subacute clinical behavior of most cases, and the poor performance status of many elderly patients, there is still controversy as to the best therapeutic approach in MDS. Histological analysis allowed two groups of MDS patients to be identified, both characterized by poor life expectancy, who could benefit from early aggressive chemotherapy.
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PMID:Prognostic relevance of histological findings on bone marrow biopsy in myelodysplastic syndromes. 844 44

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

A 52-year-old female was admitted to our hospital in August 1988, for evaluation of purpura and gingival bleeding. Hematologic examination showed mild leukocytosis (12,400/microliter) and severe thrombocytopenia (1,000/microliter). On bone marrow examination, megakaryocyte count was normal and the number of myeloblasts was increased (7.2%). Serological examination was positive for anti-nuclear antibody and anti-DNA antibody. She was diagnosed as having idiopathic or autoimmune thrombocytopenia, and received thrombocyte transfusion and gamma-globulin administration. Hematologic values improved temporarily, but leukocytosis and thrombocytopenia recurred. On the 22nd hospital day, leukocytes increased to 49,300/microliter and thrombocytes decreased to 10,000/microliter. Bone marrow myeloblasts were also increased to 18.8%, and she was suspected of having myelodysplastic syndrome. Then, hematologic values improved simultaneously, and she was discharged in November 1988. After the discharge, leukocyte count ranged from 6,000 to 16,500/microliter, but the number of bone marrow myeloblasts was normal. However, transient thrombocytopenia appeared in association with decrease or absence of bone marrow megakaryocytes and rise of platelet associated-IgG, (PA-IgG) to 99.6 ng/10(7) cells. From September to December 1989, she complained of fever, morning stiffness, multiple arthralgia, and oral ulcer. On serological findings, she was positive for LE cell. Therefore, she was diagnosed as having systemic lupus erythematosus (SLE). In January 1990, she had a high grade fever and dyspnea. Bilateral pleuritis and interstitial pneumonitis were shown on the chest roentgenogram. She received gamma-globulin administration, methylprednisolone pulse therapy, and mechanical ventilation. However, hypoxia developed rapidly, and she died of respiratory failure. Autopsy revealed severe interstitial pneumonitis, fibrinous pleuritis, fibrinous pericarditis, and vasculitis in the arcuate artery of the kidney. This is the first report of SLE complicating thrombocytopenia associated with decrease of megakaryocytes and rise of the PA-IgG, and severe leukocytosis associated with increased bone marrow myeloblasts.
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PMID:[An autopsy case of systemic lupus erythematosus complicating leukocytosis, amegakaryocytic thrombocytopenia, interstitial pneumonitis, and pleulitis]. 881 May 48


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