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          Institute: MPI für molekulare Genetik     Collection: Department of Computational Molecular Biology     Display Documents

ID: 229483.0, MPI für molekulare Genetik / Department of Computational Molecular Biology
Activation of the HIF pathway in childhood ALL, prognostic implications of VEGF
Authors:Wellmann, S.; Guschmann, M.; Griethe, W.; Eckert, C.; Stackelberg, Av; Lottaz, C.; Moderegger, E.; Einsiedel, H. G.; Eckardt, K.-U.; Henze, G.; Seeger, K.
Date of Publication (YYYY-MM-DD):2004-03-11
Title of Journal:Leukemia : the Journal of Normal and Malignant Hemopoiese ; Official Journal of the Leukemia Research Fund U.K.
Issue / Number:5
Start Page:926
End Page:933
Copyright:© 2004 Nature Publishing Group
Review Status:not specified
Audience:Experts Only
Abstract / Description:Hypoxia-inducible factor 1 (HIF-1) controls angiogenesis and glycolysis, two leading characteristics of solid tumor invasion, metastasis, and lethality. Increased angiogenesis is also found in the bone marrow (BM) of leukemias. Less is known in leukemia about the role of HIF-1 and vascular endothelial growth factor (VEGF), the most important proangiogenic target gene of HIF-1. We show by immunohistochemistry that the oxygen-regulated component of HIF-1 (HIF-1alpha) is overexpressed in clusters of leukemic cells in BM specimens of childhood acute lymphoblastic leukemia (ALL) and absent in biopsies of normal BM. Half the HIF-1alpha-positive ALL biopsies exhibited VEGF coexpression. Among 96 children with relapsed ALL, diagnostic BM aspirates with high VEGF mRNA levels were associated with a significantly lower probability of event-free survival at 3 years (0.31±0.08 vs 0.65±0.07, P=0.003). Those with poor molecular response to therapy (evaluated by MRD assessment) had 2.2-fold higher VEGF levels than those responding well to chemotherapy (P=0.005). In conclusion, the data demonstrate activation of the HIF pathway in the BM of ALL patients and indicate that the expression of HIF target genes, such as VEGF, play an important role in leukemia progression, therapy response, and outcome.
Comment of the Author/Creator:Erratum in: Leukemia. 2004 Jun;18(6):1164
External Publication Status:published
Document Type:Article
Version Comment:Automatic journal name synchronization
Communicated by:Martin Vingron
Affiliations:MPI für molekulare Genetik
External Affiliations:Department of Pediatric Oncology/Hematology, Medical University at Berlin, Berlin, Germany;
Department of Pathology, Medical University at Berlin, Berlin, Germany;
Department of Nephrology and Medical Intensive Care, Medical University at Berlin, Berlin, Germany;
Institute of Anatomy, Charité, Medical University at Berlin, Berlin, Germany.
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