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

Differentiation of essential thrombocythemia (ET) from thrombocythemias occurring in various subtypes of chronic myeloproliferative disorders (MPDs) is controversial, because of the lack of uniform clinical and morphological criteria. A retrospective clinicopathologic study was performed on 375 patients presenting with a MPD and a platelet count exceeding 500 x 10(9/)l. For comparison 35 patients with reactive thrombocytosis (RT) and five patients with a myelodysplastic syndrome (MDS-5q(-) syndrome) were enrolled into this study. In addition to a complete clinicopathological work-up, procedures included histochemical and immunological staining techniques and morphometry of bone marrow biopsies for proper evaluation of megakaryocytes (CD61) and erythroid precursors (Ret40f). Because of the high patient's age on admission, relative survival rates with corresponding disease-specific loss of life expectancy were calculated. Analysis of clinical and morphological characteristics, in particular megakaryopoiesis revealed features which enabled a clear-cut distinction between thrombocythemias in MPDs and thrombocythemic states in MDS. This rationale proved to be most important for the diagnostic discrimination of the 33 patients with initial (prefibrotic) stages of idiopathic myelofibrosis (IMF) from ET (40 patients). A new set of relevant criteria for the diagnosis of IMF with special regard to early stages and its distinction from ET has been proposed. Hemorrhagic episodes were more frequently observed in ET than in thrombocythemias associated with polycythemia vera (PV). Computation of specific loss of life expectancy revealed two extremes: thrombocythemia in CML (81%) and ET (3%), whereas thrombocythemias in PV and IMF did not show a significantly different life loss (19-22%). The revised criteria for ET, PV and IMF are reliable by taking histopathological features from bone marrow biopsies into consideration, particularly for the diagnosis of ET and its differentiation from thrombocythemias as a presenting symptom accompanying the various subtypes of MPDs.
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PMID:Clinicopathological diagnosis and differential criteria of thrombocythemias in various myeloproliferative disorders by histopathology, histochemistry and immunostaining from bone marrow biopsies. 1022 1

In order to determine the relationship between bone marrow (bm) endosteal cells (EDC) and hemopoietic progenitors, we have analyzed the immunophenotype of EDC using various antibodies (Ab) against mesenchymal antigens. The Ab were applied on paraffin sections of normal bm (iliac crest, n=17; talus, n=1; phalanx, n=1), myeloregenerative bm (after chemotherapy), and hematologic disorders (acute myeloid leukemia (AML), n=8; chronic myeloid leukemia (CML), n=6; myelodysplastic syndromes (MDS), n=14; severe aplastic anemia (SAA), n=4; essential thrombocythemia (ET), n=2; idiopathic (primary) osteomyelo-fibrosis (IMF), n=1; polycythemia vera (PV), n=1). In normal bm, EDC were found to react with Ab against vimentin, tenascin, alpha-smooth muscle actin, osteocalcin, CD51, and CD56, but did not react with Ab against CD3, CD15, CD20, CD34, CD45, CD68, or CD117. An identical phenotype of EDC was found in AML, MDS, SAA, ET, IMF, PV, myeloregenerative bm, and peripheral bones lacking active hemopoiesis (talus, phalanx). In patients with CML, EDC reacted with Ab to CD51, but did not react with Ab to CD56. Based on their unique antigen profile, EDC were enriched from normal bm by enzyme digestion and cell sorting. However, these enriched cells (CD56+, CD45-, CD34-) did not give rise to hemopoietic cells under the culture conditions used, i.e. in the presence of the growth factors IGF-1, bFGF, SCF, IL-3, and GM-CSF Together, our data do not support the hypothesis that EDC are totipotent mesenchymal progenitors giving rise to hemopoietic cells.
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PMID:Immunophenotypic characterization of human bone marrow endosteal cells. 1039 6

We reviewed the literature concerning the history of determination of the ploidy of human megakaryocytes and its relationship with diseases. The ploidy of rabbit megakaryocytes was analyzed by microspectrophotometry in 1964, and the analysis of the ploidy in human megakaryocytes was first performed in 1968. Presently, microphotometry and flow cytometry are the primary methods for the evaluation of the ploidy, but they have their merits and demerits. In the ploidy of human megakaryocytes, a peak has often been reported at 16N in healthy individuals, and the next peaks have been observed at 32N and 8N. The results of ploidy analyses have been reported by many investigators to be comparable between patients with idiopathic thrombocytopenic purpura and normal subjects, but various shifts of the peaks have also been documented. The ploidy is often reported to shift to a larger ploidy class in polycythemia vera and essential thrombocythemia, but it has invariably been reported to shift to a smaller class in chronic myelogenous leukemia. In reactive thrombocytosis, the ploidy pattern was reported to be the same as that in normal individuals by some investigators but to shift to a larger ploidy by others. These differences are considered to be due to heterogeneity of the subjects. In myelodysplastic syndrome, the ploidy shifts mostly to a smaller class, but it may show various patterns. We also reviewed the ploidy in other rare hematological disorders, the relationships of the ploidy with diabetes mellitus and atherosclerotic disorders, and its changes in the ontogeny. Details of the mechanism of polyploidization and its biological significance remain unknown, and further advances in the studies of these topics are anticipated.
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PMID:Human megakaryocyte ploidy. 1050 38

Acute leukemia and myelodysplastic syndromes are rare, but almost invariably fatal, evolutions of essential thrombocythemia (ET). Three major factors are associated with blastic transformation: cytogenetic abnormalities, myelofibrotic features, and the use of cytotoxic agents. Hematological malignancies have been reported in ET patients after treatment with alkylating agents, such as busulphan, as well as other cytoreductive drugs, such as hydroxyurea. Concerns about leukemogenicity have led some to suggest limiting the indications of these drugs to patients at higher risk of bleeding and thrombosis. Major risk factors for thrombosis are age above 60 years and a previous thrombotic event, whereas an increased bleeding tendency has been reported with platelet counts in excess of 1000-1500x10(9)/l. No myelosuppressive therapy is recommended for younger patients if they are asymptomatic or their platelet counts are below 1500x10(9)/l. The threshold of 1500x10(9)/l is controversial, however, and cytoreduction can be considered when platelets are above 1000x10(9)/l or in the presence of risk factors for cardiovascular disease. In the presence of thrombotic events or extreme thrombocytosis, young ET patients can be managed with cytoreductive agents theoretically devoid of leukemogenic risk, such as a-interferon or anagrelide. Nevertheless, the mutagenic risk of anagrelide has not been investigated in long-term follow-up studies, and the ultimate place of these 'new' drugs in the management of ET patients remains to be established in prospective and controlled clinical trials.
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PMID:Treatment of essential thrombocythemia with special emphasis on leukemogenic risk. 1052 25

Differentiation of an elevated, repeatedly determined platelet count (> or =500x10(9)/l) includes the discrimination between reactive causes generated by a variety of underlying conditions and a neoplastic myeloproliferative disorder (CMPD). In addition to clinical findings, the evolution of laboratory data during follow-up and histology of the bone marrow exerts a significant diagnostic impact. Characteristic features are not only expressed by hematopoiesis, but also by the myeloid stromal compartment. While the megakaryocyte-rich subtype of chronic myeloid leukemia (CML) and the 5q(-) syndrome (MDS) are dominated by abnormal micromegakaryocytes, in polycythemia vera (PV) this cell lineage reveals a pleomorphous appearance. In essential thrombocythemia (ET), a prevalence of giant megakaryocytes with deeply lobulated (staghorn-like) nuclei may be encountered. A clear-cut discrimination of ET from early (hypercellular) stages of idiopathic (primary) myelofibrosis (IMF) presenting with thrombocythemia becomes possible, provided the conspicuous atypical features of megakaryopoiesis characterizing the latter entity are taken into account. Moreover, CML displays a predominance of the granulocytic lineage whereas PV shows a panmyelosis or trilineage proliferation, involving erythropoiesis, in particular. In contrast, erythropoiesis is markedly reduced in CML and to a lesser degree also in IMF. In CMPDs extreme values of iron deposits may be found, ranging from a total lack (PV) to minor amounts (CML) and a normal staining reaction (ET). Similar results are exhibited regarding reticulin fibrosis, which is usually not present in ET, rarely observed in PV and detectable to a variable degree in CML and IMF.
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PMID:[Thrombocytosis versus thrombocythemia--differential diagnosis of elevated platelet count]. 1066 67

Essential thrombocythemia (ET) is a chronic myeloproliferative disorder characterized by increased risk of thrombosis and/or hemorrhages. Cytotoxic drugs are mostly used in patients at high risk for thrombotic complications, while their use is still debated in low risk patients because of the risk of leukemia or secondary neoplasm. We discuss the leukemic risk of available treatment strategies in a large cohort of patients. Over a 12 years period we treated 23 patients with busulfan (BU), 1 with pipobroman (Pi), 6 with 32P, 48 with hydroxyurea (HU) in 62 cases associated with acetyl salicylic acid (ASA) while 77 patients received ASA alone and 33 did not receive any therapy. We observed 2 cases of acute leukemia (AL) and 1 of myelodysplastic syndrome (MDS). One of these patients had been treated with 32P and Pi these after with and the other two with BU and HU. They represented 23% of all patients treated with more than 1 cytotoxic agent, 16.6% of 32P treated subjects, 4% of those with HU and 6.4% of those with BU. The case of MDS occurred in a 81 years old female and represents 4% of cases of ET over the 70 years of age. No cases of AL or MDS were observed in patients not receiving cytotoxic therapy (with or without ASA). According to our experience the use of more than one cytotoxic agent in ET confirms the increase in the risk of leukemia in these cases. However, none of the patients treated with HU alone, even for more than 10 years (12 cases) developed AL. No treatment or therapy with ASA alone may be the best choice in young patients with ET with a low risk of thrombotic complications.
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PMID:Leukemia and myelodysplasia effect of multiple cytotoxic therapy in essential thrombocythemia. 1075 89

A 28-year-old Japanese woman with suspected essential thrombocythemia (ET) had marked thrombocytosis, mild leukocytosis with normal neutrophil alkaline phosphatase activity, and no anemia. She was monitored without being given any medication. Eleven years later, complete blood counts showed no remarkable changes but some non-lobulated mononuclear megakaryocytes were found in the bone marrow. Cytogenetic analysis revealed deletion of the long arm of chromosome 5 (5q-). Subsequently, hemoglobin and platelet counts decreased gradually, splenomegaly appeared and progressed, after which myelofibrosis developed. Acute leukemia developed 16 years after the first documentation of thrombocytosis. 5q- syndrome is known to be a myelodysplastic syndrome (MDS) with unique clinical features and cases with this syndrome presenting with thrombocytosis of more than 1,000 x 10(9)/L but without anemia are rare. Furthermore, it is noteworthy that in this patient transition to acute leukemia occurred following development of myelofibrosis and marked splenomegaly, which are generally observed in blastic crises resulting from chronic myeloproliferative disorders (CMPD). The patient showed features indicative of CMPD rather than of MDS in spite of presenting with 5q- chromosomal abnormality. This case supports the concept of "mixed myelodysplastic and myeloproliferative syndromes" and suggests the possibility of the appearance of CMPD-like manifestations in 5q- syndrome.
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PMID:5q- syndrome presenting chronic myeloproliferative disorders-like manifestation: a case report. 1081 92

The objectives of this study were to expand on recent observations that have suggested decreased thrombopoietin receptor (c-Mpl) expression in megakaryocytes of patients with polycythemia vera (PV) and agnogenic myeloid metaplasia (AMM). We applied an immunoperoxidase method with anti-c-Mpl antibody to 55 bone marrow sections from previously untreated patients with chronic myeloproliferative disorder (CMPD) or myelodysplastic syndrome (MDS). These included 8 patients with PV, 15 with AMM, 9 with essential thrombocythemia, 5 with chronic myelocytic leukemia, 9 with the 5q-syndrome and 9 with MDS with fibrosis. The findings were compared with those in four patients with reactive erythrocytosis (RE), six with immune thrombocytopenic purpura (ITP) and five normal controls. Staining intensity (SI) was moderate to strong both in normal controls and in patients with RE or ITP. In contrast, SI was weak in variable proportions of the megakaryocytes in every one of the aforementioned clonal myeloid disorders. The staining pattern (SP) was relatively uniform in MDS and heterogeneous in CMPD. Neither SI nor SP was significantly correlated with certain clinical or laboratory parameters. We concluded that altered megakaryocyte c-Mpl expression may be a nonspecific phenomenon in various subtypes of both CMPD and MDS. However, the characteristic staining patterns may complement the morphological distinction between clonal and reactive myeloproliferation.
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PMID:Megakaryocyte c-Mpl expression in chronic myeloproliferative disorders and the myelodysplastic syndrome: immunoperoxidase staining patterns and clinical correlates. 1100 52

The AML1 gene, situated in 21q22, is often rearranged in acute leukemias through t(8;21) translocation, t(12;21) translocation, or less often t(3;21) translocation. Recently, point mutations in the Runt domain of the AML1 gene have also been reported in leukemia patients. Observations for mutations of the Runt domain of the AML1 gene in bone marrow cells were made in 300 patients, including 131 with acute myeloid leukemia (AML), 94 with myelodysplastic syndrome (MDS), 28 with blast crisis chronic myeloid leukemia (CML), 3 with atypical CML, 41 with acute lymphoblastic leukemia (ALL), and 3 with essential thrombocythemia (ET). Forty-one of the patients had chromosome 21 abnormalities, including t(8;21) in 6 of the patients with AML, t(12;21) in 8 patients with ALL, acquired trisomy 21 in 17 patients, tetrasomy 21 in 7 patients, and constitutional trisomy 21 (Down syndrome) in 3 patients. A point mutation was found in 14 cases (4.7%), including 9 (22%) of the 41 patients with AML of the Mo type (MoAML) (none of them had detectable chromosome 21 rearrangement) and 5 (38%) of the 13 myeloid malignancies with acquired trisomy 21 (1 M1AML, 2 M2AML, 1 ET, and 1 atypical CML). In at least 8 of 9 mutated cases of MoAML, both AML alleles were mutated: 3 patients had different stop codon mutations of the 2 AML1 alleles, and 5 patients had the same missense or stop codon mutation in both AML1 alleles, which resulted in at least 3 of the patients having duplication of the mutated allele and deletion of the normal residual allele, as shown by FISH analysis and by comparing microsatellite analyses of several chromosome 21 markers on diagnosis and remission samples. In the remaining mutated cases, with acquired trisomy 21, a missense mutation of AML1, which involved 2 of the 3 copies of the AML1 gene, was found. Four of the 7 mutated cases could be reanalyzed in complete remission, and no AML1 mutation was found, showing that mutations were acquired in the leukemic clone. In conclusion, these findings confirm the possibility of mutations of the Runt domain of the AML1 gene in leukemias, mainly in MoAML and in myeloid malignancies with acquired trisomy 21. AML1 mutations, in MoAML, involved both alleles and probably lead to nonfunctional AML1 protein. As AML1 protein regulates the expression of the myeloperoxidase gene, the relationship between AML1 mutations and Mo phenotype in AML will have to be further explored. (Blood. 2000;96:2862-2869)
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PMID:High incidence of biallelic point mutations in the Runt domain of the AML1/PEBP2 alpha B gene in Mo acute myeloid leukemia and in myeloid malignancies with acquired trisomy 21. 1102 23

Cellular and extracellular alterations of various fibrogenic cytokines have been described in a number of different chronic myeloid disorders that are associated with myelofibrosis. However, the available information related to both myelodysplastic syndrome with myelofibrosis (MDS-f) and bone marrow histochemical analysis is limited. In the current study, bone marrow immunohistochemical staining for platelet-derived growth factor, transforming growth factor (TGF)-beta, basic fibroblast growth factor (bFGF), and their receptors was performed in 9 patients with MDS-f, 9 patients with essential thrombocythemia (ET), 8 patients with 5q- syndrome, and 5 healthy control subjects. In addition, TGF-beta1 messenger RNA (mRNA) analysis was performed in 5 patients, each with MDS-f, myelofibrosis with myeloid metaplasia (MMM), polycythemia vera (PV), ET, and immune thrombocytopenic purpura, and in healthy control subjects. In general, protein and transcript expression patterns were similar to normal patterns and not significantly different among the various disease groups. The only exception was a reduced concentration of bFGF-expressing stromal cells in patients with PV, ET, and MMM.
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PMID:Bone marrow histochemical studies of fibrogenic cytokines and their receptors in myelodysplastic syndrome with myelofibrosis and related disorders. 1118 90


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