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  • Title: Fluorescence in-situ hybridization (FISH) reveals that in chronic myelogenous leukaemia (CML) following interferon-alpha therapy, normalization of megakaryocyte size is associated with the loss of bcr/abl translocation.
    Author: Thiele J, Schmitz B, Gross H, Kvasnicka HM, Niederle N, Leder LD, Fischer R.
    Journal: Histopathology; 1997 Sep; 31(3):215-21. PubMed ID: 9354890.
    Abstract:
    AIMS: 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-alpha 2b (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. 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 microns2. In untreated patients, atypical microforms (size 200 microns2) 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 microns2) reflecting a reduction in the number of micromegakaryocytes (43%). These findings were particularly conspicuous in three patients with a major to complete cytogenetic remission. 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.
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