title: Interferon therapy, but not busulfan restores normal-sized megakaryopoiesis in CML--a comparative histo- and immunomorphometric study.
abstract: To assess possible alterations of megakaryocytes associated with interferon (IFN) and busulfan (BU) therapy of Ph(1+)-CML, an immunohistochemical and morphometric study was performed on trephine biopsies of the bone marrow taken before and at varying intervals during treatment. For the identification of megakaryopoiesis and its endoreduplicative activity the monoclonal antibodies CD61 (anti-platelet glycoprotein IIIa) and PC10 raised against proliferating cell nuclear antigen (PCNA) were used. We compared 60 specimens from 20 patients following IFN alpha-2b administration (in combination with IFN gamma in seven patients) with 57 specimens from 22 patients after monotherapy with BU. A close correlation with clinical follow-up studies revealed that in the IFN-treated group the prevalence of atypical micro-megakaryocytes, usually characterizing CML, was conspicuously reduced in repeatedly taken bone marrow samples. Initially, even an increase in size which was levelled to normal values during maintenance therapy was observed. These features were most prominently expressed in the 13 patients with a complete hematologic and/or partial cytogenetic response. Associated with this phenomenon was a significant enhancement of the PCNA-labelling index which indicated a stimulation of endoreduplicative (endomitotic) activity necessary for achieving normal size and ploidy. In the second group of patients treated by BU these changes were absent. For this reason, our findings are in keeping with the assumption that during IFN treatment, there is at least partial recovery and expansion of a putative normal (Ph1-) megakaryopoiesis. In conclusion, megakaryocyte morphology, i.e. normalization in size, is thought to be a useful indicator to evaluate the response to IFN in CML patients.
authors.affiliation: Institute of Pathology, University of Cologne, Germany.
authors.forename: J
authors.initials: J
authors.lastname: Thiele
authors.forename: T
authors.initials: T
authors.lastname: Zirbes
authors.forename: H M
authors.initials: HM
authors.lastname: Kvasnicka
authors.forename: N
authors.initials: N
authors.lastname: Niederle
authors.forename: J
authors.initials: J
authors.lastname: Dammasch
authors.forename: M
authors.initials: M
authors.lastname: Schmidt
authors.forename: R
authors.initials: R
authors.lastname: Windecker
authors.forename: L D
authors.initials: LD
authors.lastname: Leder
authors.forename: V
authors.initials: V
authors.lastname: Diehl
authors.forename: R
authors.initials: R
authors.lastname: Fischer
mesh_terms: D000328:Adult; D000368:Aged; D015703:Antigens, CD / Q000276:immunology; D001707:Biopsy, Needle; D001853:Bone Marrow / Q000473:pathology; D002066:Busulfan / Q000627:therapeutic use*; D005260:Female; D006801:Humans; D019044:Image Cytometry; D007150:Immunohistochemistry; D039661:Integrin beta3; D016023:Integrins / Q000276:immunology; D016898:Interferon-alpha / Q000627:therapeutic use; D007371:Interferon-gamma / Q000627:therapeutic use; D007372:Interferons / Q000627:therapeutic use*; D015464:Leukemia, Myelogenous, Chronic, BCR-ABL Positive / Q000188:drug therapy* / Q000473:pathology*; D008297:Male; D008533:Megakaryocytes / Q000187:drug effects* / Q000473:pathology*; D008875:Middle Aged; D010980:Platelet Membrane Glycoproteins / Q000276:immunology
chemical_list: D015703:Antigens, CD; D039661:Integrin beta3; D016023:Integrins; D016898:Interferon-alpha; D010980:Platelet Membrane Glycoproteins; D007371:Interferon-gamma; D007372:Interferons; D002066:Busulfan