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  • 1
    Electronic Resource
    Electronic Resource
    Acute myelofibrosis in megakaryoblastic leukemia with translocation between chromosomes 8 and 14 (1987)
    Springer
    Journal of molecular medicine 65 (1987), S. 1034-1041 
    Details
    ISSN: 1432-1440
    Keywords: Acute myelofibrosis ; Megakaryoblastic leukemia ; Platelet peroxidase ; Cytogenetics ; β-Thromboglobulin ; Flow cytometry
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary In a 45-year-old woman with severe normochromic anemia (Hb 2.8 g%) an extensive myelofibrosis and infiltration of the bone marrow with small blasts was observed histologically. Cytochemical examination of the blasts showed a negative peroxidase and a strongly positive alpha-NE reaction. PAS reaction was slightly granular positive in the cytoplasmic protuberances of the blasts and in the platelets. Marker analysis yielded no evidence of lymphatic origin of the blasts. In flow-cytometric studies of 230,000 cells a homogeneous 2c blast population could be identified. Cytogenetic analysis revealed an abnormal pseudo-diploid karyotype characterized by 2 acrocentric marker chromosomes caused by a translocation of chromosomes 8 and 14, as usually seen in Burkitt type lymphoma. Finally the reaction product of platelet-specific peroxidase could be demonstrated in the perinuclear cisternae of the endoplasmic reticulum by electron microscopy. Highly elevated β-thromboglobulin and platelet factor 4 plasma levels were also measured. Following an ineffective treatment with daunoblastine and ARA-C, the patient died of pseudomonas aeruginosa septicemia after having received high-dose ARA-C treatment.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF01726322
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  • 2
    Electronic Resource
    Electronic Resource
    Dysregulated Mpl-Ligand production by hemopoietic cellsinduces a fatal myeloproliferative syndrome in mice (1997)
    Springer
    Hematology and cell therapy 39 (1997), S. 117-118 
    Details
    ISSN: 1279-8509
    Keywords: Retroviral transfer ; Marrow graft ; Thrombopoietin ; Hyperexpression ; Myelofibrosis
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract To evaluate the effects of long-term high-dose exposure to Mpl-ligand also called thrombopoietin (TPO), C57BL/6J murine marrow cells were infected with a retrovirus carrying the murine TPO gene. Mice were treated 4 days by 5-FU and marrow cells were then infected by coculture using a MPZen vector containing the murine TPO cDNA. Non adherent marrow cells were transplanted into lethally irradiated recipients. A majority of hematopoietic cells in the marrow, spleen, thymus and blood was transduced by the retroviral vector, one and three months after reconstitution. Plasma TPO activity in transplanted mice was extremely high (104 U/ml). A disease with two distinct steps was observed. During the two first months after transplantation, platelet (plt) and white blood cell (WBC) counts increased 4- and 10-fold, respectively. Abnormal platelet size and granules were observed. Spleen weight increased 4-fold and marrow cellularity decreased 5-fold. Histology revealed hyperplasia of the megakaryocytic and myeloid cells. Total numbers of CFU-MK and CFU-GM increased. In contrast, the hematocrit progressively fell accompanied by a decrease in the erythroblasts and CFU-E numbers. Beginning two months after transplantation, plt and WBC numbers also declined. Thrombocytopenia was noted 5 months after transplantation. The Hcts continued to decrease. Few cells were isolated from the marrow cavities and spleens. Histology revealed fibrosis of the marrow and spleen and significant osteosclerosis of the marrow. An extramedullary hematopoiesis was observed in numerous organs such as the liver or the kidney. Total numbers of progenitors were very low in hematopoietic organs. Mice died 7 months after transplantation with severe pancytopenia. Two early deaths were observed with a marked increase in blast cells. This disorder was transplantable into secondary recipients who developed an attenuated form of the disease similar to the one previously described [Yan et al (1995) Blood 86: 4025]. In conclusion, dysregulated TPO production by hemopoietic cells in mice results in a fatal myeloproliferative disease which mimics the clinical evolution of idiopathic myelofibrosis observed in man.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s00282-997-0117-1
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  • 3
    Electronic Resource
    Electronic Resource
    Human platelet alpha granules contain a nonspecific inhibitor of megakaryocyte colony formation: Its relationship to type β transforming growth factor (TGF-β) (1988)
    New York, NY [u.a.] : Wiley-Blackwell
    Journal of Cellular Physiology 134 (1988), S. 93-100 
    Details
    ISSN: 0021-9541
    Keywords: Life and Medical Sciences ; Cell & Developmental Biology
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Biology , Medicine
    Notes: Whole blood serum (WBS) and platelet-poor plasma-derived serum (PDS) from the same normal subject were compared for their abilities to support human megakaryocyte (MK) colony formation. In all cases, PDS promoted the growth of a higher number (20-50%) of MK colonies than did WBS. Increasing amounts of WBS decreased the number of colonies, whereas increasing concentration of PDS had no marked effects. Crude platelet extracts or platelet secretory products from thrombin-activated platelets also elicited an inhibition of MK colony formation in a dose-dependent manner. A complete inhibition was found for a dose equivalent to 1.109 platelets/ml and a 50% inhibition in a range of 1.107-1.108 platelets/ml. These platelet products were also inhibitory for erythroid progenitor growth. Platelets from two patients with gray platelet syndrome elicited only a minor inhibition of MK growth, suggesting that the platelet alpha granule is the origin of this inhibition. When platelet extracts were acid-treated, the biological activity of the inhibitor on CFU-MK and CFU-E growth was 20-50-fold higher. In addition, a potent stimulatory activity on the growth of day 7 CFU-GM was observed. The enhancement of biological activities by acid treatment suggests that type β transforming growth factor (TGF-β) could be involved in this platelet inhibitory activity. The homogeneous native TGF-β (from 1 pg to 1 ng/ml) produced the same effects previously induced by platelet products. It totally inhibited CFU-MK growth (at a 500 pg/ml), it inhibited CFU-E growth, and it stimulated growth of day 7 CFU-GM in the presence of a colony-stimulating factor. The inhibition of CFU-MK growth was also observed on purified progenitors. In conclusion, these results suggest that TGF-β may be implicated in negative autocrine regulation of megakaryopoiesis. However, since this molecule has ubiquitous biological activities, its physiologic relevance as a normal regulator of megakaryopoiesis requires further investigation.
    Additional Material: 7 Ill.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1002/jcp.1041340111
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