title: Reversal of bone marrow angiogenesis in chronic myeloid leukemia following imatinib mesylate (STI571) therapy.
abstract: The effect of imatinib mesylate (imatinib) therapy on angiogenesis and myelofibrosis was investigated and compared with interferon (IFN) and hydroxyurea (HU) in 98 patients with newly diagnosed Philadelphia chromosome-positive/BCR-ABL(+) (Ph(+)/BCR-ABL(+)) chronic myeloid leukemia in first chronic phase and no other pretreatment. By means of immunostaining (CD34) and morphometry, a relationship between microvessel frequency and fiber density was detectable in initial bone marrow (BM) biopsies and sequential examinations after at least 8 months of therapy. First-line monotherapy with imatinib induced a significant reduction (normalization in comparison with controls) of microvessels and reticulin fibers. In most patients, decrease in BM vascularity was associated with a complete cytogenetic response. A significant anti-angiogenic effect was also observed after HU treatment, contrasting with IFN administration or combination regimens (IFN plus HU). In conclusion, our data support the anti-angiogenic capacity of imatinib by normalization of vascularity. In contrast, hematologic response following IFN treatment is independent from BM angiogenesis.
authors.affiliation: Institute of Pathology and First Clinic of Medicine, University of Cologne, Germany. hm.kvasnicka@uni-koeln.de
authors.forename: Hans Michael
authors.initials: HM
authors.lastname: Kvasnicka
authors.forename: Juergen
authors.initials: J
authors.lastname: Thiele
authors.forename: Peter
authors.initials: P
authors.lastname: Staib
authors.forename: Annette
authors.initials: A
authors.lastname: Schmitt-Graeff
authors.forename: Martin
authors.initials: M
authors.lastname: Griesshammer
authors.forename: Jens
authors.initials: J
authors.lastname: Klose
authors.forename: Knut
authors.initials: K
authors.lastname: Engels
authors.forename: Susanne
authors.initials: S
authors.lastname: Kriener
mesh_terms: D000328:Adult; D000970:Antineoplastic Agents / Q000627:therapeutic use; D001549:Benzamides; D001853:Bone Marrow / Q000098:blood supply*; D001856:Bone Marrow Examination; D004341:Drug Evaluation; D006801:Humans; D006918:Hydroxyurea / Q000627:therapeutic use; D000068877:Imatinib Mesylate; D000077190:Interferon alpha-2; D016898:Interferon-alpha / Q000627:therapeutic use; D015464:Leukemia, Myelogenous, Chronic, BCR-ABL Positive / Q000188:drug therapy* / Q000473:pathology*; D008833:Microcirculation; D009389:Neovascularization, Pathologic / Q000188:drug therapy*; D010879:Piperazines / Q000627:therapeutic use*; D011743:Pyrimidines / Q000627:therapeutic use*; D011994:Recombinant Proteins; D012074:Remission Induction; D012189:Retrospective Studies
chemical_list: D000970:Antineoplastic Agents; D001549:Benzamides; D000077190:Interferon alpha-2; D016898:Interferon-alpha; D010879:Piperazines; D011743:Pyrimidines; D011994:Recombinant Proteins; D000068877:Imatinib Mesylate; D006918:Hydroxyurea