AML-1 is required for megakaryocytic maturation and lymphocytic differentiation, but not for maintenance of hematopoietic stem cells in adult hematopoiesis.

Motoshi Ichikawa, Takashi Asai, Toshiki Saito, Sachiko Seo, Ieharu Yamazaki, Tetsuya Yamagata, Kinuko Mitani, Shigeru Chiba, Seishi Ogawa, Mineo Kurokawa, Hisamaru Hirai

Department of Hematology and Oncology, Graduate School of Medicine, University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo, 113-8655, Japan.

Nature medicine 2004 Mar

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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-2alphaB). In vitro studies and findings in human diseases, including leukemias, myelodysplastic syndromes and familial platelet disorder with predisposition to acute myeloid leukemia (AML), 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 method. 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.

Citation

Motoshi Ichikawa, Takashi Asai, Toshiki Saito, Sachiko Seo, Ieharu Yamazaki, Tetsuya Yamagata, Kinuko Mitani, Shigeru Chiba, Seishi Ogawa, Mineo Kurokawa, Hisamaru Hirai. AML-1 is required for megakaryocytic maturation and lymphocytic differentiation, but not for maintenance of hematopoietic stem cells in adult hematopoiesis. Nature medicine. 2004 Mar;10(3):299-304