Reversal of bone marrow angiogenesis in chronic myeloid leukemia following imatinib mesylate (STI571) therapy.
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.
Kvasnicka
Hans Michael
HM
Institute of Pathology and First Clinic of Medicine, University of Cologne, Germany. hm.kvasnicka@uni-koeln.de
Thiele
Juergen
J
Staib
Peter
P
Schmitt-Graeff
Annette
A
Griesshammer
Martin
M
Klose
Jens
J
Engels
Knut
K
Kriener
Susanne
S
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
D000970:Antineoplastic Agents; D001549:Benzamides; D000077190:Interferon alpha-2; D016898:Interferon-alpha; D010879:Piperazines; D011743:Pyrimidines; D011994:Recombinant Proteins; D000068877:Imatinib Mesylate; D006918:Hydroxyurea