Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0023418 (leukemia)
 93,477 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The activity of platelet factor 4 (FP4) was examined in 37 patients affected with blastic leukaemia, in 16 patients with blastic crisis in chronic myeloid leukaemia and in 2 patients with Willebrand's syndrome. The real activity of FP4 determined by modifying the method according to NIEWIAROWSKI after a complete lysis of granular membrances by means of triton X-100 was found to be lowered in 9 patients affected with blastic leukaemia, in 5 patients with blastic crisis and in two patients with Willebrand's syndrome. Presuming that a maximal FP4 release of the irreversible platelet aggregation must be obtained, which corresponds to the real activity, the author has examined the apparent activity of FP4 released from the aggregated platelets with the help of her own method. In this way the quality of the release reaction from the platelets can indirectly be characterized with their extremely important role for haemostasis. Whereas in exacerbated myeloid leukaemia and Willebrand's syndrome the apparent activity will correspond to the real one, there is a severe specific disturbance of the platelet release response in blastic leukaemia. The platelet aggregation is incomplete caused by the derailment of the energy metabolism and the disturbance of the adenine nucleotides, thus causing an apparent as well as a real FP4 deficiency which can be brought into the same line with pathogenesis of thrombopathy in blastic leukaemia.
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PMID:[Liberation of anti-heparin activity during platelet aggregation in patients with blastic leukosis and blastic crisis of chronic myelosis]. 5 Sep 73

Venous thrombosis is a common complication of total parenteral nutrition. We report a case of priapism in a 40-year-old man after administration of total parenteral nutrition for chronic idiopathic intestinal pseudo-obstruction. The patient received glucose, amino acids, and 20% fat emulsion; 12 hours after administration, the patient complained of a persistent, painful penile erection lasting 5 hours. Bilateral corpora cavernosa spongiosum shunts achieved immediate and sustained detumescence, but the patient remained impotent. There was no history of penile or pelvic trauma, hemoglobinopathy, coagulopathy, venous thrombosis, or leukemia. The medical literature describes seven other cases of priapism related to total parenteral nutrition. All of the patients received 20% fat emulsion; two patients developed priapism during the weekly infusion of fat emulsion. Among the multiple factors that can favor thrombosis and therefore priapism during total parenteral nutrition, fat infusion appears to be the most important. Three different mechanisms have been postulated: increase in blood coagulability, effects on red blood cells, and fat embolism. In this patient, platelet function was estimated in vivo by the levels of antiheparin platelet factor 4 and beta-thromboglobulin. These two parameters were both elevated before 20% lipid emulsion and were even higher after the 20% fat-emulsion infusion. Therefore, even if a direct thromboplastic effect is possible, 20% fat emulsion increases platelet activity, which was already high in our patient, and thereby favors priapism.
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PMID:Priapism in a patient treated with total parenteral nutrition. 155 16

A new human leukemia cell line with megakaryocytic features, designated UT-7, was established from the bone marrow of a patient with acute megakaryoblastic leukemia. Surface marker analysis revealed that the majority of the cells reacted with monoclonal antibodies against platelet glycoprotein Ib (CD42b), glycoprotein IIb/IIIa (CD41a), MY 7 (CD13), MY 9 (CD33), and glycophorin A antigens. Cytogenetic analysis showed a human male near-tetraploid karyotype with a modal chromosome number of 92-96. Flow cytometry-derived DNA histograms demonstrated that the majority of the cells spontaneously contained 4 N DNA ploidy levels. Ultrastructural study showed that platelet peroxidase activity was weakly positive but myeloperoxidase activity was negative. Ferritin and theta-granule, which have been used as ultrastructural markers for the erythroid lineage, could not be detected. In response to phorbol myristate acetate, platelet factor 4 and beta-thromboglobulin, which were specifically synthesized in the process of megakaryocyte maturation, dramatically increased in UT-7 cells. This was accompanied by an increase in cell size, ploidy level, platelet peroxidase activity, and the surface density of glycoprotein IIb/IIIa antigen. These findings suggest that UT-7 is a new leukemic cell line with megakaryocytic features and with the potential to differentiate into cells with more mature megakaryocytic properties in response to phorbol myristate acetate. This cell line showed strict dependency on interleukin 3 (IL-3), granulocyte-macrophage colony-stimulating factor, or erythropoietin. The maximal effective doses of IL-3, granulocyte-macrophage colony-stimulating factor, and erythropoietin for proliferation in liquid culture were 10 units/ml, 1 ng/ml, and 1 unit/ml, respectively. These concentrations were comparable to the doses that maximally stimulate the clonal growth of normal hemopoietic cells. IL-6 could stimulate the proliferation of UT-7 cells but not maintain the line in long-term culture. UT-7 cells may be a useful model for (a) the analysis of gene regulation of megakaryocytic maturation-associated proteins expressed in the process of megakaryocytic differentiation and (b) the study of signal transduction of hemopoietic factors associated with megakaryocytopoiesis.
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PMID:Establishment and characterization of a human leukemic cell line with megakaryocytic features: dependency on granulocyte-macrophage colony-stimulating factor, interleukin 3, or erythropoietin for growth and survival. 182 23

A 61-year-old man with Philadelphia chromosome-positive chronic myelogenous leukemia developed megakaryoblastic leukemia. In the blast phase, his blast cells showed undifferentiated megakaryoblastic characteristics with no alpha-granules or demarcation membranes but with detectable platelet peroxidase (PPO) activity and surface glycoprotein (GP) IIb/IIIa. The patient has remained reasonably well for at least 12 months after blastic crisis, and 6-mercaptopurine alone has been effective in controlling leukocytosis and megakaryoblast proliferation. The expression of mRNA for platelet-specific proteins, such as GPIIb and platelet factor 4 (PF4), was studied in the patient's blast cells by the Northern blot analysis. Both GPIIb and PF4 mRNA were detected in the blast cells. Cytoplasmic maturation occurs later than the synthesis of the surface GP during megakaryocyte maturation. Therefore, PF4 mRNA expression should be a marker of mature megakaryoblasts. The PF4 mRNA expression in megakaryoblastic leukemia may indicate that a patient will have long survival and a good response to chemotherapy.
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PMID:Platelet factor 4 mRNA expression in cells from a patient with megakaryoblastic crisis of chronic myelogenous leukemia. 199 Dec 66

Platelet function and the clinical course of the disease were prospectively investigated in 29 patients with myeloproliferative disorders. Serial determinations (median: 5 investigations per patient within 17 months) of platelet aggregation, plasma and intraplatelet concentrations of beta-thromboglobulin (beta TG) and platelet factor 4 (PF4), and of fibrinopeptide A (FPA) plasma levels were carried out. In the chronic phase of polycythaemia vera, patients with thrombohaemorrhagic complications during the study period had higher platelet count, more severe platelet aggregation defects, and increased plasma levels of beta TG and FPA compared to patients without complications. However, thrombohaemorrhagic complications were not predicted by changes in these parameters in the individual patient during the chronic disease phase. When patients with chronic myelogenous leukaemia entered blast crisis, bleeding complications were related to thrombocytopenia, impaired platelet function and low intraplatelet concentrations of beta TG and PF4. Cytoreduction by chemotherapy in the chronic phase of CML did not alter beta TG and PF4 plasma levels, whereas treatment of polycythaemia rubra vera by venesection favourably influenced platelet alpha-granule secretion and increased intraplatelet concentrations of beta TG and PF4.
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PMID:A prospective study of haemostatic parameters in relation to the clinical course of myeloproliferative disorders. 214 44

We report a patient with acute myelofibrosis (AM) in whom a megakaryocytic origin was demonstrated after conventional microscopy, investigation with monoclonal antibodies directed against the glycoprotein complex IIb/IIIa (CD41a) and the platelet peroxidase (PPO) reaction. Thus, a diagnosis of acute megakaryoblastic leukemia (AMGL) was made. It is now known that this megakaryoblastic proliferation is responsible for myelofibrosis as an increased release of platelet-derived growth factor (PDGF), beta-thromboglobulin (BTG), and platelet factor 4 (PF4) develops because ineffective megakaryocytopoiesis and failure of these clonal populations to store the mentioned substances in their alpha granules. At the time of diagnosis, the plasma concentrations of BTG and PF4 were measured and were found to be high. Thus, an increased PDGF level was indirectly assumed, with the subsequent fibroblast stimulation. After treatment with low dose cytosine arabinoside, a clinical, analytical and histological remission was achieved, with a return of BTG and PF4 values to the normal range. It was therefore concluded that the follow up of these parameters is useful for the diagnosis and the establishment of remission criteria in these patients.
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PMID:[Beta-thromboglobulin and platelet factor 4 in a follow-up of acute myelofibrosis (megakaryoblastic leukemia)]. 214 51

Immunofluorescence staining of buffy coat smears from a patient with chronic myelogenous leukemia in accelerated phase showed that approximately 13% of all nucleated cells contained von Willebrand protein and, therefore, appeared to be of megakaryocytic origin. This was confirmed by positive staining with antisera against platelet factor 4 and platelet glycoproteins. Short-term cultures of the buffy coat, which lacked endothelial cells, were metabolically labeled with [35S]methionine, and von Willebrand protein was immunopurified from cell lysates and culture medium. Cultures from this patient synthesized and secreted von Willebrand protein, in contrast with cultures from other patients with leukemia, who lacked circulating megakaryocytes, and from normal volunteers. The subunit composition of the megakaryocytic von Willebrand protein was very similar to that of human umbilical vein endothelial cells. The size of the processed subunit (220 kD) and of the cellular (260 kD) and secreted (275 kD) precursors from the two cell types were indistinguishable by gel electrophoresis. Furthermore, the ratio of precursor to processed subunit and the pattern of cellular and secreted nonreduced multimers were very similar. It appears, therefore, that the processing steps in biosynthesis of von Willebrand protein used by the megakaryocytes are very similar to those of umbilical vein endothelial cells.
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PMID:Biosynthesis of von Willebrand protein by human megakaryocytes. 241 71

An interferon-inducible cytokine, IP-10, containing homology to a family of proteins having chemotactic (platelet factor 4, beta-thromboglobulin) and mitogenic (connective tissue-activating peptide III) activities has been mapped to chromosome 4 at band q21, a locus associated with an acute monocytic/B-lymphocyte lineage leukemia that exhibits the nonrandom translocation t(4;11)(q21;q23). In situ hybridization of t(4;11)(q21;q23)-carrying leukemic cells revealed that the IP-10 gene is proximal to the breakpoint of this translocation. No DNA rearrangement was evident when the IP-10 gene was hybridized to genomic DNA isolated from two patients' leukemic cells that contain t(4;11)(q21;q23). However, restriction fragment length polymorphism in the 5' region of the IP-10 gene was detected. The ETS1 protooncogene is located at 11q23 and is known to translocate to chromosome 4 in t(4;11) (q21;q23) and into the interferon gene cluster in (9;11) (p22;q23). Both translocations are associated with acute monocytic leukemia. These results suggest a model in which juxtaposition of genetic loci regulated by antiproliferative signals, such as interferon, next to an oncogene, like ETS1, could effectively short circuit homeostatic control circuits and contribute to the neoplastic state.
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PMID:Interferon-inducible gene maps to a chromosomal band associated with a (4;11) translocation in acute leukemia cells. 243 86

We report that highly purified human platelet factor 4 (PF4) inhibits human megakaryocytopoiesis in vitro. At greater than or equal to 25 micrograms/ml, PF4 inhibited megakaryocyte colony formation approximately 80% in unstimulated cultures, and approximately 58% in cultures containing recombinant human IL 3 and granulocyte-macrophage colony-stimulating factor. Because PF4 (25 micrograms/ml) had no effect on either myeloid or erythroid colony formation lineage specificity of this effect was suggested. A synthetic COOH-terminal PF4 peptide of 24, but not 13 residues, also inhibited megakaryocyte colony formation, whereas a synthetic 18-residue beta-thromboglobulin (beta-TG) peptide and native beta-TG had no such effect when assayed at similar concentrations. The mechanism of PF4-mediated inhibition was investigated. First, we enumerated total cell number, and examined cell maturation in control colonies (n = 200) and colonies (n = 100) that arose in PF4-containing cultures. Total cells per colony did not differ dramatically in the two groups (6.1 +/- 3.0 vs. 4.2 +/- 1.6, respectively), but the numbers of mature large cells per colony was significantly decreased in the presence of PF4 when compared with controls (1.6 +/- 1.5 vs. 3.9 +/- 2.3; P less than 0.001). Second, by using the human leukemia cell line HEL as a model for primitive megakaryocytic cells, we studied the effect of PF4 on cell doubling time, on the expression of both growth-regulated (H3, p53, c-myc,and c-myb), and non-growth-regulated (beta 2-microglobulin) genes. At high concentrations of native PF4 (50 micrograms/ml), no effect on cell doubling time, or H3 or p53 expression was discerned. In contrast, c-myc and c-myb were both upregulated. These results suggested the PF4 inhibited colony formation by impeding cell maturation, as opposed to cell proliferation, perhaps by inducing expression of c-myc and c-myb. The ability of PF4 to inhibit a normal cell maturation function was then tested. Megakaryocytes were incubated in synthetic PF4, or beta-TG peptides for 18 h and effect on Factor V steady-state mRNA levels was determined in 600 individual cells by in situ hybridization. beta-TG peptide had no effect on FV mRNA levels, whereas a approximately 60% decrease in expression of Factor V mRNA was found in megakaryocytes exposed to greater than or equal 100 ng/ml synthetic COOH-terminal PF4 peptide. Accordingly, PF4 modulates megakaryocyte maturation in vitro, and may function as a negative autocrine regulator of human megakaryocytopoiesis.
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PMID:Inhibition of human megakaryocytopoiesis in vitro by platelet factor 4 (PF4) and a synthetic COOH-terminal PF4 peptide. 252 11

Two cases of myelofibrosis are reported, one corresponding to a chronic idiopathic myelofibrosis and another to an acute myelofibrosis or megakaryoblastic leukemia (AMGL). According to current knowledge, the origin of fibrosis in these disorders is a megakaryoblastic/megakaryocytic proliferation in the bone marrow. These megakaryocytic clonal populations result in an ineffective megakaryocytopoiesis and in an inability to store beta-thromboglobulin (BTG), platelet factor 4 (PlF4) and platelet derived growth factor (PDGF) in the alpha granules, whereby their release is increased. Both PDGF, a powerful stimulator of fibroblastic activity, and PlF4, a collagenase inhibitor, cooperate in the development of myelofibrosis. Owing to its action inducing cellular differentiation towards the monocytic-macrophagic line, which secretes collagenases and inhibits megakaryocyte proliferation, treatment with 1,25-dihydroxyvitamin D3 was attempted in both cases, 2.5 micrograms daily for 6 months. Satisfactory results were achieved.
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PMID:[Beneficial effect of 1,25-dihydroxyvitamin D3 in the treatment of myelofibrosis]. 281 98


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