Runx1/AML-1 ranks as a master regulator of adult hematopoiesis.

Runx1 (AML-1) is a critical gene involved in human leukemogenesis, originally identified at the 21q22 breakpoint of the leukemic translocations of t(8;21)(q21;q22), and is thought to be involved in as much as 25% of human leukemia. It encodes a transcription factor that has close homology to a Drosophila protein, runt, and is found to play essential roles in regulation of hematopoietic systems. Really a gene disruption experiment unequivocally shows that Runx1 is absolutely required for the establishment of definitive or adult-type hematopoiesis. Moreover, accumulated evidence from a number of in vitro studies and findings in patients with familial platelet disorder with predisposition to acute myelogenous leukemia (FPD/AML) strongly suggests that it also commits to the control of hematopoietic system in adult life, although the in depth analysis of its roles in adult hematopoiesis has been largely hampered by premature lethality of Runx1-null animals. Recently we have developed conditional knockout mice in which Runx1 is disrupted specifically in hematopoietic compartments after birth and dissected its roles in adult hematopoiesis. Notably, in these mice, maturation of megakaryocytes and development of both T and B lymphocytes were severely impaired, whereas hematopoietic progenitors were maintained or even expanded with apparently normal myeloid and erythroid differentiation in the periphery and bone marrow. Our findings clearly demonstrated differential requirement of Runx1 in stem cell development and in its maintenance together with multi-modal functions of this transcription factor that are critically required for maturation of megakaryocytes and lymphocyte development, also providing a novel insight into how deeply amd meticulously Runx1 is involved in regulation of mammalian hematopoiesis.