@article{f1bdfbc33a8649ec8e0cbcfde675cebb,
title = "AML1, the target of multiple chromosomal translocations in human leukemia, is essential for normal fetal liver hematopoiesis",
abstract = "The AML1-CBFβ 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 cells 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.",
author = "Tsukasa Okuda and {Van Deursen}, Jan and Hiebert, {Scott W.} and Gerard Grosveld and Downing, {James R.}",
note = "Funding Information: The authors would like to thank Dr. Shouli Yang, Paul Conn, Cristy Nagy, John Swift, and Lawryn Kasper for excellent technical assistance; Drs. Alessandra d'Azzo and X.-Y. Zhou for helping in establishing ES cell cultures; Drs. Dave Witte and Holly Soares for assistance in the morphologic evaluation of embryos; Drs. Sheila Shurtleff, Noel Lenny, Ross Fisher, and John Cunningham for helpful discussions and critical reading of the manuscript; Dr. Sue Vallance for editorial assistance; and Dr. Bart Williams for helpful comments on the GPI analysis. This work was supported by National Institutes of Health (NIH) grant RO1-64140 and American Cancer Society grants CB-39 and JFRA-591 to S. W. H., NIH Cancer Center CORE Grant CA-21765, and the American Lebanese and Syrian Associated Charities of St. Jude Children's Research Hospital. ",
year = "1996",
month = jan,
day = "26",
doi = "10.1016/S0092-8674(00)80986-1",
language = "English (US)",
volume = "84",
pages = "321--330",
journal = "Cell",
issn = "0092-8674",
publisher = "Cell Press",
number = "2",
}