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  • 1
    ISSN: 1365-2559
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: In addition to predominant granulocytic proliferation, bone marrow morphology in Philadelphia chromosome positive (Ph1+) CML is characterized by atypical dwarf or microforms of megakaryocytes. However, following therapy with interferon-α2b (IFN), these micromegakaryocytes occur less frequently. The purpose of this study was to elucidate whether the reappearance of normal megakaryocytes may be associated also with a reduction of the bcr/abl-positive cell clone.〈section xml:id="abs1-2"〉〈title type="main"〉Methods and results:Fluorescence in-situ hybridization (FISH) technique in combination with immunomorphometry (CD61) was performed on trephine biopsies. A total of 311 CD61-positive megakaryocytes, including precursors and atypical microforms, were evaluated in pre-treatment specimens derived from 11 patients with Ph1+ CML. A specific fusion site marking the bcr/abl translocation was found in 87% of megakaryocytes which showed a size of 169 ± 35 μm2. In untreated patients, atypical microforms (size 200 μm2) were observed in 66% of the total megakaryocytic population. Following IFN therapy 369 megakaryocytes could be analysed in sequential examinations and were found to display a significant decrease (63%) in positive fusion signals. In addition there was also a significant enhancement in average size (252 ± 66 μm2) reflecting a reduction in the number of micromegakaryocytes (43%). These findings were particularly conspicuous in three patients with a major to complete cytogenetic remission.〈section xml:id="abs1-3"〉〈title type="main"〉Conclusions:A normalization of megakaryocyte size following IFN therapy in CML is significantly associated with a loss of the bcr/abl translocation site and therefore indicates a (partial) recovery of normal haematopoiesis.
    Type of Medium: Electronic Resource
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  • 2
    ISSN: 1365-2559
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: Myelodysplastic syndromes, AIDS-related myelopathy and non-specific inflammatory reactions (mostly rheumatoid myelitis) are characterized by normo- to hypercellular bone marrow, but frequently display cytopenias in the peripheral blood. In the current study we have addressed the question whether this situation reflects an increased programmed cell death in haemopoiesis. For this purpose, the in situ end-labelling technique was applied to formalin-fixed and paraffin-embedded trephine biopsies derived from patients and a control group without any haematological disorder. Results were evaluated by morphometry. Significantly more apoptotic cell death was observed in the haemopoietic marrow of patients with either disease. Using double-immunohistochemistry with the monoclonal antibody PG-M1 (CD68), we were able to demonstrate that approximately one third of the apoptotic cells were ingested by macrophages. Our findings are in keeping with previously published data that postulated increased frequencies of macrophages in these disorders as well as raised serum levels of TNF-α.
    Type of Medium: Electronic Resource
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