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Surgical Neurology Branch, National Institute of Neurological Disorders and Stroke [A. O. V., S. F., S-Y. J., K. Y., B. I., Y-S. L., D. B., R. L., E. H. O., Z. Z.] and Molecular and Clinical Hematology Branch, National Institutes of Diabetes, Digestive and Kidney Diseases [R. S., G. R.], NIH, Bethesda, Maryland 20892
The nature of the cell responsible for von Hippel-Lindau (VHL) disease-associated tumor formation has been controversial for decades. We demonstrate that VHL disease-associated central nervous system tumors are composed of developmentally arrested angioblasts that coexpress erythropoietin (Epo) and Epo receptor. The angioblasts are capable of differentiating into RBCs via formation of blood islands with extramedullary hematopoiesis. Because of VHL deficiency, Epo receptor-expressing, developmentally arrested angioblasts simultaneously coexpress Epo, which may represent a crucial pathogenetic step in tumor formation.
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