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Query: UMLS:C0023418 (leukemia)
 93,477 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The use of Wright-Giemsa-stained smears alone for the classification of acute leukemias often proves unsatisfactory. Some cases of M1, M5a, M7, and L2 are morphologically similar. In such cases, cytochemical stains can provide an inexpensive and available diagnostic tool. M1 is positive for SBB and MPO. M5a is usually NSE positive, whereas SBB and MPO are negative. M7 usually is ANA esterase, PAS, and AP reactive, and do not stain with SBB, MPO, and ANB esterases. The megakaryocytic lineage usually is confirmed by ultrastructural cytochemistry for PPO or immunocytochemistry for platelet glycoproteins and von Willebrand factor. PAS block positivity and AP dotlike reactivity are suggestive of lymphoid lineage. NSE stains are useful in differentiating M2 from M4. Morphologic and cytochemical techniques also can suggest the presence of certain chromosomal abnormalities such as t(8;21) and inv(16), which may have an influence on prognosis. Because not all cases of acute leukemia are easily subtyped by morphology and cytochemistry, immunophenotyping, karyotyping, and molecular analysis of DNA and RNA of leukemia cells also may be required to define cell lineage.
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PMID:The use of cytochemical procedures in the diagnosis and management of acute and chronic myeloid leukemia. 170 64

The commitment process of a human megakaryoblastic cell line (MEG-O1) induced with phorbol ester, TPA, was investigated with special reference to glycoprotein (GP) IIb/IIIa expression, multinuclear formation, and DNA replication. TPA (10(-7) mol/L) completely inhibited cellular division in MEG-O1, but did not suppress de novo DNA synthesis. Two days' culture with 10(-7) mol/L TPA was sufficient for MEG-O1 cells to initiate an irreversible commitment process. These cells could not resume cell growth and expressed GP IIb/IIIa antigen; some of them showed multinuclear form and DNA polyploidy even after removal of TPA from the culture medium. DNA histogram analysis showed that, upon treatment with TPA, the percentage of cells whose DNA ploidy was more than 8N was 5 to 10 times higher than that of control cells. Precise analysis using cell size fractionation by centrifugal elutriation method showed that there was strong correlation between the percentage of multinuclear cells and DNA polyploidy in TPA-treated cells. The percentage and staining intensity of GP IIb/IIIa and other megakaryocytic phenotypes such as von Willebrand factor and PAS staining were highest in large multinuclear cell populations, suggesting that these cells are the most differentiated population in this system. In TPA-treated cells, the activity of DNA polymerase alpha, a marker for cell growth, remained at the same level as in control cells. Aphidicolin, a specific inhibitor of DNA polymerase alpha, completely inhibited the differentiation induction of MEG-O1 cells with TPA measured by either GP IIb/IIIa expression or multinuclear cell formation. Therefore, DNA replication appears to be involved in the process of phenotypic expression as well as endomitosis in megakaryocyte differentiation of MEG-O1 cells. Aphidicolin was also effective in inhibiting megakaryocytic differentiation of other leukemia cell lines such as human erythroleukemia (HEL) and K562 cell lines induced with TPA, suggesting the close interplay of DNA replication and phenotypic expression in megakaryopoiesis.
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PMID:Aphidicolin, an inhibitor of DNA replication, blocks the TPA-induced differentiation of a human megakaryoblastic cell line, MEG-O1. 174 84

Veno occlusive disease (VOD) is a frequent complication of allogenic bone marrow transplantation (BMT) for which no predictive blood markers are available. 39 patients grafted for severe aplastic anemia (18), and leukemia (21) were prospectively studied. Of the 39 patients, 5 leukemic patients, but no aplastic patients developed VOD. In all the 5 patients with VOD complications we demonstrated a decrease in factor VII and in protein C before the clinical onset of the disease and before any changes in hepatic enzymes were observed. This decrease is the earliest sign of hepatic involvement by the VOD suggesting that the determination of Factor VII and protein C can be used as a prediction test to identify the patients who are at risk of developing VOD after transplantation. In addition, a toxicity of the endothelial cells was suggested by the observed increase in von Willebrand factor and in Serum Angiotensin Converting Enzyme. Signs of endothelial toxicity was more pronounced in leukemic than in aplastic patients.
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PMID:Liver veno-occlusive disease after bone marrow transplantation changes in coagulation parameters and endothelial markers. 132 36

Functionally active thrombomodulin (TM) was expressed in human megakaryoblastic leukemia (MEG-01s) cells. We examined the effect of agents that increased the intracellular concentration of cAMP on the expression of TM by these cells. N6,O2-dibutyryl cAMP (dbcAMP) markedly enhanced TM antigen, activity, and mRNA level in MEG-01s cells. Other agents, 8-bromo-cAMP (8BrcAMP), forskolin, and prostaglandin E1 were also effective for the enhancement. Moreover, similar enhancement of TM by these agents was also observed in another human leukemia cell line, HEL, which has megakaryocytic markers. In contrast to the marked enhancement of TM expression by these agents, the expression of the other megakaryocytic markers including platelet glycoproteins IIb/IIIa, Ib, von Willebrand factor and beta-thromboglobulin was not stimulated in MEG-01s or HEL cells. These results suggest that expression of TM is rather specifically regulated by cAMP in human megakaryocytes.
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PMID:Enhanced expression of thrombomodulin by intracellular cyclic AMP-increasing agents in two human megakaryoblastic leukemia cell lines. 216 72

The quantitative evolution of endothelial cells (ECs) in Dexter-type human long-term bone marrow cultures (HLTBMCs) was investigated. Using monoclonal antibodies directed against von Willebrand factor (vWF) and against membrane antigens (EN-4 and PAL-E), a low percentage--usually less than 1% of stromal cells--of ECs was detected in all confluent cultures established from 11 different bone marrow samples. Generally these cells are not associated directly with the areas of myelopoiesis ("cobblestone areas"). ECs cannot be demonstrated in the adherent layer of most young, non-confluent, and of some old, HLTBMCs. In some instances, morphological features suggestive of dynamic behavior were seen (sprouting, canal formation). In addition, a very low proportion of vWF-positive megakaryocytic cells was found in 4 of 11 cultures, always in direct contact with the stromal fibroblastic cells.
Leukemia 1989 Jan
PMID:A quantitative and dynamic study of endothelial cells and megakaryocytes in human long-term bone marrow cultures. 246 57

We analyzed the clinical and laboratory features of eight children (median age, 20 months; range, 13 months to 11 years) with acute megakaryocytic leukemia (M7) and compared the findings with those reported in the literature. The diagnosis was supported by ultrastructural examination for platelet peroxidase or immunophenotyping for glycoprotein IIb/IIIa or the von Willebrand factor protein. Two patients had Down's syndrome. Initial findings included anemia (in all patients), thrombocytopenia (in six), myelofibrosis (in three), lytic bone lesions (in two), and pronounced leukocytosis (in one). Stem cell culture studies of peripheral blood specimens revealed an aberrant phenotype of the megakaryocytes in one patient and reversal to a normal pattern after successful therapy. Remission was achieved in seven of the eight patients after aggressive chemotherapy, and four patients remained in remission 27 to 57 months after diagnosis. Three of these four patients underwent allogeneic bone marrow transplantation. M7 leukemia is not infrequent in children younger than 3 years of age, especially in those with Down's syndrome. The availability of monoclonal antibodies specific to restricted antigens of the megakaryocytic lineage has made the diagnosis of M7 leukemia both possible and practical.
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PMID:Acute megakaryocytic leukemia (M7) in children. 259 24

The localization of three known alpha-granule proteins, thrombospondin (TSP), von Willebrand factor (vWF), and fibrinogen (Fg) has been studied in human megakaryocytes (MK) by immunofluorescence and immunoelectron microscopy. For this study, highly purified populations of MK were prepared from human bone marrow either by counterflow centrifugal elutriation or by cell culture from normal subjects and from two patients with megakaryoblastic leukemia. In normal bone marrow immature MK, TSP, and vWF were observed in the Golgi-associated vesicles and in small immature alpha-granules; in mature MK, they were found in the matrix of the mature large alpha-granules. Surprisingly, Fg was detected neither in the Golgi area, nor in the small precursors of alpha-granules; it was only found in the mature alpha-granules but this labeling was generally weaker than in blood platelets. In order to confirm these differences between the expression of Fg and vWF or TSP additional studies were performed on cultured maturing MK: immunofluorescent and ultrastructural immunogold labeling confirmed that vWF appeared early in the maturation while the same immature MK were negative for Fg. In the late maturation stage, the three proteins were detected in the alpha-granules. In order to know whether Fg was lately synthesized or endocytosed from the outside medium, normal MK were grown in the presence of either normal or afibrinogenemic plasma, and normal serum. Fg was detected only in the alpha-granules of MK grown in normal plasma. Similar results were observed with malignant MK, whose maturation was independent of the culture conditions. In conclusion, this study brings immunocytochemical evidence that vWF and TSP are synthesized by immature MK, whereas Fg appears later in the MK alpha-granules and its expression is dependent of the presence of an exogenous Fg source.
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PMID:Uncoordinated expression of fibrinogen compared with thrombospondin and von Willebrand factor in maturing human megakaryocytes. 264 67

Amphotropic murine leukemia virus pseudotypes of murine sarcoma viruses containing the ras or mos oncogenes were constructed to permit efficient introduction of the sarcoma virus genome into early-passage human umbilical vein endothelial cells. The resulting cell lines were morphologically and phenotypically unchanged, retaining properties characteristic of differentiated endothelial cells. For example, the cells in a Kirsten sarcoma virus-modified line were found to biosynthesize and secrete von Willebrand factor in both a constitutive and regulated manner, and they contained ultrastructurally identifiable Weibel-Palade bodies, an endothelial cell-specific organelle. In contrast to the parent cultures, sarcoma virus-modified cells were able to proliferate indefinitely in culture. Examination of both Kirsten sarcoma and Moloney leukemia virus-modified lines indicated that the immortalized cells retained a diploid female karyotype after over 18 months in culture. In addition, the sarcoma virus-modified cells were able to grow independently of added endothelial cell growth factor. This growth factor autonomy does not appear to be due to autocrine production of a biologically cross-reactive growth factor. These immortal, virus-modified endothelial cells express large amounts of sarcoma virus-specific mRNA but no detectable helper virus or transforming virus activity. This technique for immortalization of primary human cells without alteration of the differentiated characteristics of the cell type is readily applied to a variety of human cell types. Moreover, the ability to separate the immortalizing and transforming activities of viral oncogenes should provide further understanding as to mechanisms of oncogene action.
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PMID:Immortalization of human endothelial cells by murine sarcoma viruses, without morphologic transformation. 282 2

A new human megakaryocytic cell line (Dami) has been established from the blood of a patient with megakaryoblastic leukemia. The Dami cells grow primarily in suspension with a doubling time of 24 to 30 hours. By light and electron microscopy, the Dami cells range in size from 12 to 120 micron in diameter and have lobulated nuclei characteristic of megakaryocytes. At least 89% of the cells react with monoclonal antibodies against platelet glycoproteins (GP) Ib and IIB/IIIa, and glycophorin. The cells do not react with antibodies against lymphoid, monocyte, granulocyte, or macrophage antigens. Thirteen percent of the cells become polyploid, spontaneously achieving greater than 4N DNA ploidy levels. In response to phorbol myristate acetate (PMA), the proportion of cells with ploidy levels greater than 4N increased threefold and could be separated into discrete ploidy groups. PMA also increased the expression of GPIb, the GPIIb/GPIIIa complex,l and von Willebrand factor. Cytogenetic analysis revealed a human male hyperdiploid karyotype with a modal chromosome number of 54 to 64 and several consistent clonal chromosomal abnormalities. These included a partial deletion of chromosome 5 and a translocation involving chromosome 3. In contrast to other megakaryocytic cell lines in which only a small portion of the cells express the megakaryocytic phenotype, nearly all of the Dami cells express platelet glycoproteins. Thus, the Dami cells provide a superior model in which to study human megakaryocyte biochemistry and differentiation.
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PMID:Characterization of a new megakaryocytic cell line: the Dami cell. 319 74

We studied the multimeric composition of plasma von Willebrand factor (vWf) in 26 patients with chronic myelocytic leukaemia (CML); 13 in chronic phase, 8 in blast crisis, 5 in both chronic phase and blast crisis. The relative amount of large (multimer band greater than or equal to 11) multimers calculated by densitometer scan following SDS-agarose gel electrophoresis was 14.6 +/- 2.9% (mean +/- SD) in normal controls, 8.7 +/- 4.7% in chronic phase and 15.0 +/- 5.2% in blast crisis. CML patients in chronic phase (but not in blast crisis) had a significantly lower percentage of large multimers than normal controls (p less than 0.001). The relative amount of large multimers was positively correlated with a ratio of ristocetin cofactor/vWf antigen (p less than 0.005), and was negatively correlated with platelet count (p less than 0.001), WBC count (p less than 0.05) and granulocyte count (p less than 0.05). We conclude that some patients with CML, especially in chronic phase, lack large multimers. The negative correlation of the relative amount of large multimers with platelet and granulocyte count suggests that large multimers may be consumed in high platelet count states or degraded by protease(s) from increased blood cells.
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PMID:Multimeric composition of plasma von Willebrand factor in chronic myelocytic leukaemia. 326 24


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