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

The clinical, hematologic, and histologic features of acute megakaryoblastic leukemia are described for an 8-year-old female Domestic Shorthair cat, a 3-year-old female mixed-breed dog, and a 3-year-old male German Shepherd Dog. The neoplastic cells were characterized as belonging to the megakaryocytic lineage. The following techniques were used: electron microscopy; detection of antibodies against human von Willebrand factor (vWF) and human platelet glycoprotein GP IIIa using a modified avidin biotin peroxidase complex technique on formalin-fixed paraffin sections; and enzyme histochemical methods on plastic sections for alkaline phosphatase, acid phosphatase, myeloperoxidase, alpha-naphthyl acetate esterase, alpha-naphthyl butyrate esterase, naphthol AS acetate esterase, and naphthol AS-D chloroacetate esterase. In addition, benign megakaryocytic cells, platelets, and neoplastic cells were labeled with lectins that have partially been shown to bind to platelet glycoproteins of other species. In healthy cats and dogs, the megakaryocytes and platelets reacted with lectins PSA, LCA, PHA-L, and WGA. Megakaryocytes and platelets from healthy cats were also labeled by lectin PNA. The lectins PHA-L and WGA reacted with neoplastic cells from the cat and both dogs. Lectin PNA bound to neoplastic cells from the cat, and lectins PSA, LCA, and SBA bound to neoplastic cells from both dogs. For the retrospective examination of paraffin-embedded material, the detection of vWF and GP IIIa appears to be the most reliable method for the identification of megakaryocytic cells.
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PMID:Acute megakaryoblastic leukemia in one cat and two dogs. 847 Mar 39

Selection of an optimal promoter is necessary for efficient expression of foreign genes with vaccinia virus. Since a variety of powerful (homologous) vaccinia virus promoters and foreign (heterologous) promoter systems have been described for use in vaccinia, we have addressed the question of whether a general rule exists that allows the prediction of the optimal promoter/gene combination. We have compared the expression properties of four secreted proteins, the human blood clotting factor IX (FIX), the human blood glycoprotein Protein S (ProtS), the human von Willebrand factor (vWF), and the Hepatitis B virus (HBV) middle surface glycoprotein preS2, with proteins that were reported not to be secreted, the HBV large surface glycoprotein preS1 and the murine leukemia virus (MuLV) BM-5 Eco gag protein. In addition, we have included in our study an internal control protein, the vaccinia virus p11 protein, to monitor possible side effects of the promoter system used. Genes encoding the foreign proteins were placed either under control of a synthetic vaccinia virus early/late promoter (selP) or under control of the bacteriophage T7 promoter (T7/emc system). The secreted proteins were more efficiently expressed when fused to the homologous promoter. Direct comparison of the two promoters indicated that the expression level ranged between 1.4 (ProtS) and 3.9 (FIX)-fold higher with the selP than with the T7 promoter. In contrast, the cell-associated HBV preS1 was more efficiently expressed under the T7 promoter and the MuLV BM-5 Eco gag polypeptide was expressed equally well from both promoters. These data indicate that a careful prediction of optimal promoter/foreign gene combinations for the vaccinia virus expression system is possible. The choice of the optimal promoter/expression system is based on a simple classification scheme, discriminating secreted and nonsecreted proteins.
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PMID:Requirements for optimal expression of secreted and nonsecreted recombinant proteins in vaccinia virus systems. 853 47

L-Asparaginase treatment of leukemia patients causes hemostatic problems. To investigate whether L-asparaginase influences coagulation studies, 63 blood samples of 21 healthy male donors were incubated with L-asparaginase for 30 min at room temperature. After treatment with 100 IU/ml L-asparaginase plasma fibrinogen (P = 0.002), plasma antithrombin (P = 0.0002), plasma protein C (P = 0.0004), and plasma plasminogen (P = 0.0039) were decreased compared with controls. In contrast, a significant increase in plasma von Willebrand factor antigen (P = 0.08) and plasma thromboglobulin (P = 0.005) was observed. The decrease in plasma anti-thrombin (P = 0.001), plasma protein C (P = 0.0003), and plasma plasminogen (P = 0.0043) was also measurable after 0.05 IU/ml asparaginase treatment. The incubation with L-asparaginase was similar to the normal time from blood sampling to testing and hence the results suggest that L-asparaginase may directly attack proteins of the coagulation system during the interval between sampling and assay.
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PMID:Asparaginase decreases clotting factors in vitro: a possible pitfall? 856 77

Plasma von Willebrand factor (VWF) was investigated in five patients with acute promyelocytic leukaemia (APL) before and after administration of the differentiating agent all-trans-retinoic acid (ATRA). The purpose of this study was to see how the proteolytic state associated with APL affects VWF structure and function and whether ATRA reverses any abnormality. At the onset of APL, multimeric analysis of plasma VWF revealed a lack of the largest multimers. After ATRA, there was a progressive correction of the multimeric pattern in all cases, with transient appearance of ultralarge multimers in two cases. Proteolysis was investigated with immunopurified and reduced VWF from each patient's plasma. This was electrophoresed and probed with two monoclonal antibodies that identify the 225 kD native subunit and the three native fragments of 189, 176 and 140 kD and differentiate novel proteolytic fragments produced by different proteinases. At the onset of APL, the 225 kD native subunit was relatively decreased, with the appearance of an array of novel VWF proteolytic fragments, ranging in size from <140 to <225 kD. These novel fragments observed in patients were similar to those produced in vitro by digestion of purified VWF with plasmin or elastase. After ATRA therapy, proteolysis diminished progressively in parallel with the improvement of other haemostatic measurements, but persisted to some extent. We conclude that VWF proteolysis in APL is produced by plasmin and elastase. Changes of VWF structure and function might adversely affect haemostasis in APL. Therefore, improvement of VWF after ATRA administration might explain in part the effectiveness of this drug in reducing haemorrhagic complications.
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PMID:Proteolysis of von Willebrand factor is decreased in acute promyelocytic leukaemia by treatment with all-trans-retinoic acid. 861 45

We have previously reported that propolypeptide of von Willebrand factor (pp-vWF) promotes melanoma cell adhesion in a beta1 integrin-dependent manner. In this report, we identified the alpha subunit of the cell adhesion receptor for pp-vWF as alpha4. Human leukemia cell lines that express alpha4beta1 integrin (very late antigen-4, VLA-4), but not cell lines which lack VLA-4, attached well to pp-vWF substrate and these adhesions were completely inhibited by anti-alpha4 integrin monoclonal antibody HP2/1. Adhesion of mouse melanoma expressing alpha4 integrin was also inhibited by anti-mouse alpha4 mAb PS/2. Furthermore, transfection of human alpha4 cDNA into alpha4(-) Chinese hamster ovary cells resulted in an acquisition of adhesive activity to pp-vWF, indicating that pp-vWF is a ligand for VLA-4 integrin. Using a recombinant fragment of pp-vWF, the cell attachment site was shown to be located within amino acid residues 376-455 of pp-vWF. A series of synthetic peptides covering this region were tested for the ability to promote cell attachment and a 15-residue peptide designated T2-15 (DCQDHSFSIVIETVQ, residues numbered 395-409) promoted VLA-4 dependent cell adhesion. The peptide was also capable of inhibiting cell adhesion to pp-vWF, suggesting that this sequence represents the cell attachment site. By affinity chromatography using peptide T2-15-Sepharose, it was found that alpha4beta1 integrin complex from extracts of surface iodinated B16 cells specifically bound to the peptide. These results strongly suggest that pp-vWF is a novel physiological ligand for VLA-4.
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PMID:Propolypeptide of von Willebrand factor is a novel ligand for very late antigen-4 integrin. 907 71

Megakaryocytic cell lines, established from the blood of patients with leukaemia, provide us with a unique opportunity to study the proliferation, differentiation and maturation of megakaryocytes. Eighteen human and three animal cell lines that express some megakaryocytic features have been described in the literature. Many of these cell lines have primitive multiphenotypic properties of erythroid, myeloid and megakaryocytic cells, while some show more restricted megakaryocyte-specific markers. The most consistent cell marker of megakaryocytic cell lines is the presence of platelet membrane glycoprotein (GPIIb-IIIa) in human cell lines and that of acetylcholinesterase in mouse or rat cell lines. The expressions of GPIb, von Willebrand factor and platelet peroxidase are variable among different cell lines, perhaps reflecting different stages of differentiation or a neoplastic nature of immortal cell lines. Treatment of many of these cell lines with phorbol esters leads to enhanced expression of the megakaryocytic programme.
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PMID:Megakaryocytic cell lines. 915 15

A human megakaryocyte cell line (B1647) has been established from bone marrow cells obtained from a patient with acute myelogenous leukaemia (FAB M2). The cells were CD34-, CD33+, HLA-DR+, CD38+, and expressed the immunophenotypic markers of the megakaryocyte lineage (CD41 and von Willebrand factor). Moreover the cells expressed the c-mpl (thrombopoietin receptor) mRNA and protein. On the other hand, the B1647 cells also possessed erythroid lineage characteristics: the vast majority of cells were glycophorin positive, and about 10% of unstimulated cells stained with an anti-globin gamma chain MoAb. In addition, S1 protection analysis demonstrated expression of beta-globin mRNA, and Epo receptor (Epo-R) protein was detected by cytofluorimetric assay. Several growth factors, when tested alone or in combination, failed to influence the B1647 cell growth. A significant increase of cell proliferation was observed only after the addition, in serum-free culture, of recombinant human megakaryocyte growth development factor (MGDF), a recombinant c-mpl ligand encompassing the receptor-binding domain and identical to thrombopoietin (TPO), at concentrations ranging from 0.01 to 1 ng/ml. Interestingly, MGDF failed to induce megakaryocytic differentiation of the B1647 cells, but significantly increased the synthesis of the globin gamma-chain. B1647 cells could be a useful model for studying the biological effect of TPO on common megakaryocyte and erythroid progenitors.
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PMID:An erythroid and megakaryocytic common precursor cell line (B1647) expressing both c-mpl and erythropoietin receptor (Epo-R) proliferates and modifies globin chain synthesis in response to megakaryocyte growth and development factor (MGDF) but not to erythropoietin (Epo). 933 7

Although most of the initial studies in angiogenesis were done on solid tumors, there is now data suggesting the importance of angiogenesis in hematologic malignancies. We estimated bone marrow microvessel density before autologous stem cell transplantation and at the time of response in 13 patients with myeloma (seven complete and six partial responders) using an immunohistochemical stain for factor VIII-related antigen (von Willebrand factor). Baseline microvessel density was significantly different between bone marrow samples from patients with myeloma and morphologically normal, staging marrows from patients with limited stage Hodgkin's disease, mean (+/- s.d.) 294 (+/-115)/mm2 vs 93 (+/-26/mm2, respectively, P = 0.001. After transplantation, microvessel density continued to be high in myeloma samples compared to samples from control patients with limited stage Hodgkin's disease, mean (+/- s.d.) 230 (+/-68)/mm2, P = 0.003. There was no difference in microvessel density at the time of complete or partial response compared to values prior to transplantation. This report confirms that increased angiogenesis is found in myeloma bone marrow prior to transplantation, and suggests that increased angiogenesis persists even after complete response.
Leukemia 1999 Mar
PMID:Bone marrow angiogenesis in patients achieving complete response after stem cell transplantation for multiple myeloma. 1008 38

We previously reported that MOLT-3 human lymphocyte-like leukemia cells adhere to tissue-type transglutaminase (tTG) through the integrin alpha(4)beta(1). We now report that G-361 human melanoma cells also adhere to tTG, although they do not express alpha(4)beta(1). G-361 cells utilize two additional integrins, alpha(9)beta(1) and alpha(5)beta(1) to adhere to tTG. Furthermore, blood coagulation factor XIII (FXIII), another member of the transglutaminase family that is highly homologous to tTG, and propolypeptide of von Willebrand factor (pp-vWF) also promoted cell adhesion through alpha(9)beta(1) or alpha(4)beta(1) in G-361 or MOLT-3 cells, respectively. In the case of pp-vWF, alpha(9)beta(1) and alpha(4)beta(1) both bind to the same site, comprised of 15 amino acid residues and designated T2-15. Moreover, SW480 human colon cancer cells stably transfected to express alpha(9)beta(1), but not mock transfectants, adhered to tTG, FXIII, pp-vWF, and T2-15/bovine serum albumin conjugate. These data identify tTG, FXIII, and pp-vWF as shared ligands for the integrins alpha(9)beta(1) and alpha(4)beta(1). This report is the first to unambiguously show that these two integrins share the same cell adhesion site within one protein and provides strong support for classifying alpha(9)beta(1-) and alpha(4)-integrins as functionally related members of an integrin subfamily.
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PMID:Tissue transglutaminase, coagulation factor XIII, and the pro-polypeptide of von Willebrand factor are all ligands for the integrins alpha 9beta 1 and alpha 4beta 1. 1081 92

Recent studies investigating thrombotic thrombocytopenic purpura (TTP) have implicated abnormal plasma von Willebrand factor (vWF)-cleaving metalloprotease activity in this disorder. It has been proposed that a metalloprotease cleaves unusually large (UL) multimers of vWF, which enter the circulation from the endothelium. Abnormal metalloprotease activity could result in ULvWF, which could participate in TTP. However, the diagnostic specificity of abnormalities in the plasma metalloprotease activity has not been established. A prospective study of vWF protease activity was performed using samples from 20 healthy controls, 20 patients with acute TTP, 20 patients with immune idiopathic thrombocytopenic purpura (ITP), 10 patients with disseminated intravascular thrombocytopenia (DIC), 10 patients with systemic lupus erythematosus (SLE,) and 5 thrombocytopenic patients with leukemia. Studies were performed blinded to the diagnosis. Samples from hospitalized patients with normal platelet counts were also tested. The vWF digests and multimer analysis were done using previously described methods. Six laboratory personnel independently scored each of the multimer gels. Reduced protease activity was observed in 9 of 20 patients with TTP. Reduced activity was also observed in 6 of 20 patients with ITP, 6 of 10 patients with DIC, 5 of 10 patients with SLE, 1 of 5 patients with leukemia, 2 of 20 healthy controls, and 3 of 25 hospitalized patients. This study indicates that abnormalities of vWF protease activity are not restricted to patients with the diagnosis of TTP.
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PMID:Decreased von Willebrand factor protease activity associated with thrombocytopenic disorders. 1153 19


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