AML-1 is required for megakaryocytic maturation and lymphocytic differentiation, but not for mainten
Author: ["Motoshi Ichikawa","Takashi Asai","Toshiki Saito","Go Yamamoto","Sachiko Seo","Ieharu Yamazaki","Tetsuya Yamagata","Kinuko Mitani","Shigeru Chiba","Hisamaru Hirai","Seishi Ogawa","Mineo Kurokawa"]
Publication: Nature Medicine
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Abstract
Embryonic development of multilineage hematopoiesis requires the precisely regulated expression of lineage-specific transcription factors, including AML-1 (encoded by Runx1; also known as CBFA-2 or PEBP-2αB)1,2,3,4,5. In vitro studies and findings in human diseases, including leukemias6,7, myelodysplastic syndromes8 and familial platelet disorder with predisposition to acute myeloid leukemia (AML)9, suggest that AML-1 has a pivotal role in adult hematopoiesis. However, this role has not been fully uncovered in vivo because of the embryonic lethality of Runx1 knockout in mice. Here we assess the requirement of AML-1/Runx1 in adult hematopoiesis using an inducible gene-targeting method10. In the absence of AML-1, hematopoietic progenitors were fully maintained with normal myeloid cell development. However, AML-1-deficient bone marrow showed inhibition of megakaryocytic maturation, increased hematopoietic progenitor cells and defective T- and B-lymphocyte development. AML-1 is thus required for maturation of megakaryocytes and differentiation of T and B cells, but not for maintenance of hematopoietic stem cells (HSCs) in adult hematopoiesis.
Cite this article
Ichikawa, M., Asai, T., Saito, T. et al. AML-1 is required for megakaryocytic maturation and lymphocytic differentiation, but not for maintenance of hematopoietic stem cells in adult hematopoiesis. Nat Med 10, 299–304 (2004). https://doi.org/10.1038/nm997
