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.
abstract: OBJECTIVE
  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.
  
  
  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.
authors.affiliation: Institute of Pathology, University of Cologne, Germany.
authors.forename: J
authors.initials: J
authors.lastname: Thiele
authors.forename: B
authors.initials: B
authors.lastname: Schmitz
authors.forename: H
authors.initials: H
authors.lastname: Gross
authors.forename: H M
authors.initials: HM
authors.lastname: Kvasnicka
authors.forename: N
authors.initials: N
authors.lastname: Niederle
authors.forename: L D
authors.initials: LD
authors.lastname: Leder
authors.forename: R
authors.initials: R
authors.lastname: Fischer
mesh_terms: D016044:Fusion Proteins, bcr-abl; D006801:Humans; D016898:Interferon-alpha / Q000627:therapeutic use*; D015464:Leukemia, Myelogenous, Chronic, BCR-ABL Positive / Q000188:drug therapy*; D008533:Megakaryocytes / Q000473:pathology
chemical_list: D016898:Interferon-alpha; D016044:Fusion Proteins, bcr-abl