[Therapy-related changes of angiogenesis in Philadelphia chromosome positive chronic myelogenous leukemia]

Abstract

To elucidate the effect of first-line treatment with interferon (IFN), hydroxyurea (HU) and the tyrosine kinase inhibitor imatinib (STI571) on angiogenesis, we studied bone marrow (BM) biopsies in 104 patients with chronic myelogenous leukemia (CML) and 138 patients before and after allogeneic BM transplantation (BMT). After immunostaining (CD34) and morphometric analysis in comparison with a control group, CML specimens showed an increased vascularity and conspicuous morphological abnormalities of microvessels. A close relationship between microvessels and fiber density was detectable in initial biopsies and also in repeatedly performed examinations following therapy. Monotherapy by imatinib and HU generated a significant reduction of microvessels and reticulin fibers in contrast to changes after IFN administration or combination regimens of IFN and HU. A persistence of numerical and structural anomalies of vasculature was observable even several months after BMT. These anomalies shed some light on disturbances of the stroma compartment after myeloablative therapy. The relationship between BM vascularity and fibers is probably dependent on concomitant changes of megakaryopoiesis as the source of various mediators involved in the development of myelofibrosis and neo-angiogenesis acting within a complex functional network.