title: Characterization of an acute micromegakaryocytic leukaemia: evidence for the pathogenesis of myelofibrosis.
abstract: The current hypothesis for the pathogenesis of myelofibrosis involves the intramedullary release of growth factors from defective or abnormal megakaryocytes. We describe a case of an acute micromegakaryocytic leukaemia, in a patient with chronic myelofibrosis, that provides additional evidence for this concept. The micromegakaryocytes, which reached 223 x 10(9)/l, were characterized morphologically by both light and electron microscopy, immunocytochemically and by platelet peroxidase activity. The cells were shown to have a mature cytoplasm, containing alpha granules and the associated proteins; vWF:Ag, fibrinogen, fibronectin and protein S. DNA analysis, by both a Seescan Solitaire Plus image analysis system and flow cytometry, revealed nuclear immaturity, with 92% of cells being diploid. Serum markers of connective tissue synthesis, namely carboxy terminal peptide of procollagen I (PICP), procollagen terminal peptide III (PIIIP) and laminin all increased significantly following transformation and were associated with an increase in platelet-derived growth factor (PDGF) and transforming growth factor-beta (TGF-beta). These observations support the current hypothesis for bone marrow fibrosis formation and provide, for the first time, a link between in vivo growth factor release, bone marrow stromal turnover and megakaryocyte mass. In addition, the release of biologically active TGF-beta may explain both the increased fibronectin and angiogenesis characteristic of myelofibrotic bone marrow.
authors.affiliation: Department of Haematology, Northern General Hospital, Sheffield.
authors.forename: J T
authors.initials: JT
authors.lastname: Reilly
authors.forename: D
authors.initials: D
authors.lastname: Barnett
authors.forename: G
authors.initials: G
authors.lastname: Dolan
authors.forename: P
authors.initials: P
authors.lastname: Forrest
authors.forename: J
authors.initials: J
authors.lastname: Eastham
authors.forename: A
authors.initials: A
authors.lastname: Smith
mesh_terms: D005260:Female; D006801:Humans; D007797:Laminin / Q000096:biosynthesis; D007947:Leukemia, Megakaryoblastic, Acute / Q000097:blood / Q000150:complications* / Q000473:pathology; D008533:Megakaryocytes / Q000648:ultrastructure; D008854:Microscopy, Electron; D008875:Middle Aged; D010446:Peptide Fragments / Q000097:blood; D010982:Platelet-Derived Growth Factor / Q000096:biosynthesis; D055728:Primary Myelofibrosis / Q000209:etiology*; D011347:Procollagen / Q000097:blood; D016212:Transforming Growth Factor beta / Q000096:biosynthesis
chemical_list: D007797:Laminin; D010446:Peptide Fragments; D010982:Platelet-Derived Growth Factor; D011347:Procollagen; D016212:Transforming Growth Factor beta; C041876:procollagen Type III-N-terminal peptide; C042813:procollagen type I carboxy terminal peptide