Hemangioblasts representing a functional endothelio-hematopoietic entity in ontogeny, postnatal life, and CML neovasculogenesis.

The life-long interdependencies/interactions between hemato- and endotheliopoiesis suggest that they form a supplementary functional entity. This view is compatible with the concept of stem cell plasticity as a reversible continuum and is substantiated by the common hematopoietic-endothelial stem cell, i.e., hemangioblasts, with bidirectional, reversible gene transcription and persistence in postnatal life. Indeed, embryonal stem cells/hemangioblasts appear to form a reservior in the adult with the possibility of dedifferentiation of more differentiated progenitor cells back to hemangioblasts. The recent detection of BCR/ABL fusion proteins in endothelial cells during vascular neoangiogenesis in CML suggests that endothelial cells are part of the neoplastic clone, and extends the concept of a functional entity to include CML angiogenesis. Thus, hemangioblasts rather than committed hematopoietic stem cells appear to be target cells for the first oncogenic hit in CML, which could occur as early as during the first steps of embryonal stem cell differentiation towards hemato-endotheliopoiesis and/or in hemangioblasts persisting in adults. The relation of the other leukemias to hemangioblasts is not known.