AML1, the target of multiple chromosomal translocations in human leukemia, is essential for normal fetal liver hematopoiesis.

Okuda T, van Deursen J, Hiebert SW, Grosveld G, Downing JR
Cell. 1996 84 (2): 321-30

PMID: 8565077 · DOI:10.1016/s0092-8674(00)80986-1

The AML1-CBF beta transcription factor is the most frequent target of chromosomal rearrangements in human leukemia. To investigate its normal function, we generated mice lacking AML1. Embryos with homozygous mutations in AML1 showed normal morphogenesis and yolk sac-derived erythropoiesis, but lacked fetal liver hematopoiesis and died around E12.5. Sequentially targeted AML1-/-es cell retained their capacity to differentiate into primitive erythroid cells in vitro; however, no myeloid or erythroid progenitors of definitive hematopoietic origin were detected in either the yolk sac or fetal livers of mutant embryos. Moreover, this hematopoietic defect was intrinsic to the stem cells in that AML1-/-ES cells failed to contribute to hematopoiesis in chimeric animals. These results suggest that AML1-regulated target genes are essential for definitive hematopoiesis of all lineages.

MeSH Terms (25)

Animals Base Sequence Cells, Cultured Chimera Core Binding Factor Alpha 2 Subunit Core Binding Factors DNA-Binding Proteins Embryonic and Fetal Development Gene Expression Regulation, Developmental Gene Targeting Hematopoiesis Hematopoietic Stem Cells Humans Leukemia, Myeloid Liver Mice Mice, Inbred C57BL Molecular Sequence Data Neoplasm Proteins Proto-Oncogene Proteins RNA, Messenger Sequence Homology, Amino Acid Transcription Factors Translocation, Genetic Yolk Sac

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