title: Increased angiogenesis-associated poor outcome in acute lymphoblastic leukemia: a single center study.
abstract: Angiogenesis in solid tumors is important for tumor growth, invasion, and metastasis. However, angiogenesis plays also an important role in hematological malignancies. We have analyzed the expression of vascular endothelial growth factor (VEGF) in the leukemic blast cells and microvessel density (MVD) in the bone marrow biopsy samples of the patients with acute lymphoblastic leukemia (ALL). Bone marrow MVD of the patients with ALL was significantly higher compared with normal controls and complete remission (P<0.001), but slightly lower than in patients with relapsed ALL (P>0.05). The bone marrow blast VEGF expression was significantly higher in newly diagnosed ALL patients, with predominant strong VEGF expression as compared with complete remission patients (who had negative or weak VEGF expression) (P<0.05), whereas initial values were slightly lower than in relapsed patients. There was a strong positive correlation between VEGF expression and MVD at presentation of ALL. Stronger expression of VEGF on blast cells indicates shorter overall survival in ALL. Furthermore, initial values of MVD had positive correlation with overall survival and leukemia-free survival (P=0.024 and P=0.017, respectively). Our data suggest that increased angiogenesis (confirmed by immunohistochemical expression of VEGF in leukemic blasts), and MVD may play an important role in the pathophysiology of ALL with prognostic implications. Thus, targeting VEGF pathway may bring the new approach for ALL treatment-using antiangiogenic drugs and tyrosine kinase inhibitors in combination with standard chemotherapy regimens.
authors.affiliation: Clinic for Hematology, Clinical Center of Serbia, Belgrade, Serbia. bb.lena@gmail.com
authors.forename: Milena
authors.initials: M
authors.lastname: Todorovic
authors.forename: Ziv
authors.initials: Z
authors.lastname: Radisavljevic
authors.forename: Bela
authors.initials: B
authors.lastname: Balint
authors.forename: Bosko
authors.initials: B
authors.lastname: Andjelic
authors.forename: Vera
authors.initials: V
authors.lastname: Todorovic
authors.forename: Maja Perunicic
authors.initials: MP
authors.lastname: Jovanovic
authors.forename: Biljana
authors.initials: B
authors.lastname: Mihaljevic
mesh_terms: D000328:Adult; D001853:Bone Marrow / Q000098:blood supply* / Q000378:metabolism* / Q000473:pathology; D005260:Female; D015870:Gene Expression; D006801:Humans; D008297:Male; D055806:Microvessels / Q000378:metabolism / Q000473:pathology; D008875:Middle Aged; D009389:Neovascularization, Pathologic / Q000175:diagnosis* / Q000235:genetics; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000175:diagnosis* / Q000235:genetics / Q000401:mortality / Q000473:pathology; D011379:Prognosis; D012008:Recurrence; D012074:Remission Induction; D016019:Survival Analysis; D042461:Vascular Endothelial Growth Factor A / Q000235:genetics*
chemical_list: C467484:VEGFA protein, human; D042461:Vascular Endothelial Growth Factor A