Mzf1 controls cell proliferation and tumorigenesis

MZF1 is a transcription factor belonging to the Kruppel family of zinc fing er proteins, expressed in totipotent hemopoietic cells as well as in myeloi d progenitors. Here we have inactivated Mzfi1 by gene targeting. Mzf1(-/-) mice develop lethal neoplasias characterized by the infiltration and comple te disruption of the liver architecture by a monomorphic population of cell s of myeloid origin reminiscent of human chloromas. Mzf1(-/-) inactivation results in a striking increase of the autonomous cell proliferation and of the ability of Mzf1(-/-) hemopoietic progenitors to sustain long-term hemop oiesis. These findings demonstrate that Mzf1 can act as a tumor/growth supp ressor in the hemopoietic compartment.