title: Megakaryocyte features and bcr/abl translocation in chronic myeloid leukemia following imatinib mesylate (STI571) therapy--a fluorescence in-situ hybridization study.
abstract: Following therapy with imatinib (STI571) hematologic and cytogenetic response in chronic myeloid leukemia (CML) is associated with conspicuous alterations of bone marrow (BM) morphology. Besides reduction of cellularity and fibrosis, small megakaryocytes characteristic for this disorder were replaced by large, normally appearing cells of this lineage. However, it is not known whether and to which extent these changes are accompanied by a loss of the bcr/abl translocation. Therefore an immunohistochemical (CD61) and fluorescence in-situ hybridization (FISH) study was performed on sequential BM biopsies in 5 patients with CML receiving STI571 without any pretreatment. Morphometric analysis revealed that the prevalent population of 47% micromegakaryocytes (size < or = 150 microm2) was significantly reduced (15%) during therapy and that a conspicuous shift to medium-sized and large megakaryocytes occurred. According to FISH analysis in the initial BM biopsy sections 71% of all myeloid cells exhibited the bcr/abl gene and concerning megakaryopoiesis about 65% of the prominent micromegakaryocytes displayed positive signals. After treatment this peculiar cell population decreased significantly while the emerging large megakaryocytes (52%) totally lacked a bcr/abl labeling. Because cytogenetic response and reduction of micromegakaryocytes seem to be linked, this feature may be useful to monitor therapeutic efficacy by evaluating BM morphology.
authors.affiliation: Institute of Pathology, University of Cologne, Germany. j.thiele@uni-koeln.de
authors.forename: Juergen
authors.initials: J
authors.lastname: Thiele
authors.forename: Hans Michael
authors.initials: HM
authors.lastname: Kvasnicka
authors.forename: Eva
authors.initials: E
authors.lastname: Varus
authors.forename: Esther
authors.initials: E
authors.lastname: Ollig
authors.forename: Annette
authors.initials: A
authors.lastname: Schmitt-Graeff
authors.forename: Peter
authors.initials: P
authors.lastname: Staib
authors.forename: Martin
authors.initials: M
authors.lastname: Griesshammer
mesh_terms: D000328:Adult; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D001549:Benzamides; D001706:Biopsy; D001853:Bone Marrow / Q000473:pathology; D005260:Female; D016044:Fusion Proteins, bcr-abl / Q000235:genetics*; D006801:Humans; D000068877:Imatinib Mesylate; D017404:In Situ Hybridization, Fluorescence / Q000379:methods; D015464:Leukemia, Myelogenous, Chronic, BCR-ABL Positive / Q000188:drug therapy* / Q000235:genetics* / Q000473:pathology; D008297:Male; D008533:Megakaryocytes / Q000473:pathology*; D010879:Piperazines / Q000627:therapeutic use*; D011505:Protein-Tyrosine Kinases / Q000037:antagonists & inhibitors; D011743:Pyrimidines / Q000627:therapeutic use*; D014178:Translocation, Genetic
chemical_list: D000970:Antineoplastic Agents; D001549:Benzamides; D010879:Piperazines; D011743:Pyrimidines; D000068877:Imatinib Mesylate; D011505:Protein-Tyrosine Kinases; D016044:Fusion Proteins, bcr-abl