The biology of astrocytoma: lessons learned from chronic myelogenous leukemia--hypothesis

Chronic myelogenous leukemia (CML) is an example of a "well-differentiated" neoplasm that develops following neoplastic transformation of a precursor cell. The biology of astrocytic neoplasms can be interpreted in light of concepts that have emerged from studies of the myeloproliferative disorders. Astrocytomas may arise from a pluripotential precursor cell whose progeny, although transformed, retain the ability to differentiate, and do so along astrocytic lines. The result is a neoplasm composed of "mature" tumor cells, similar one to another, and resembling normal astrocytes. Malignant change, like blast crisis in CML, then occurs as a consequence of further molecular genetic events leading to accelerated growth and maturation arrest in a previously differentiating neoplastic cell. This hypothesis challenges the conventional view that astrocytomas arise from astrocytes and that malignant change occurs as a result of dedifferentiation. Extensions of this hypothesis may be relevant to the biology of other glial tumors.