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AML-1 is required for megakaryocytic maturation and lymphocytic differentiation, but not for maintenance of hematopoietic stem cells in adult hematopoiesis.
- Source :
-
Nature medicine [Nat Med] 2004 Mar; Vol. 10 (3), pp. 299-304. Date of Electronic Publication: 2004 Feb 15. - Publication Year :
- 2004
-
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-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.
- Subjects :
- Adult
Animals
Bone Marrow Cells cytology
Bone Marrow Cells metabolism
Cell Lineage
Cell Size
Core Binding Factor Alpha 2 Subunit
DNA-Binding Proteins genetics
Gene Targeting methods
Hematopoietic Stem Cells cytology
Humans
Lymphocytes cytology
Megakaryocytes cytology
Mice
Mice, Inbred Strains
Mice, Transgenic
Proto-Oncogene Proteins genetics
Transcription Factors genetics
Cell Differentiation physiology
DNA-Binding Proteins metabolism
Hematopoiesis physiology
Hematopoietic Stem Cells physiology
Lymphocytes physiology
Megakaryocytes physiology
Proto-Oncogene Proteins metabolism
Transcription Factors metabolism
Subjects
Details
- Language :
- English
- ISSN :
- 1078-8956
- Volume :
- 10
- Issue :
- 3
- Database :
- MEDLINE
- Journal :
- Nature medicine
- Publication Type :
- Academic Journal
- Accession number :
- 14966519
- Full Text :
- https://doi.org/10.1038/nm997