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

Tsukasa Okuda, Jan Van Deursen, Scott W. Hiebert, Gerard Grosveld, James R. Downing

Research output: Contribution to journalArticle

1476 Citations (Scopus)

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.

Original languageEnglish (US)
Pages (from-to)321-330
Number of pages10
JournalCell
Volume84
Issue number2
DOIs
StatePublished - Jan 26 1996
Externally publishedYes

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Genetic Translocation
Hematopoiesis
Liver
Yolk Sac
Leukemia
Embryonic Structures
Stem cells
Erythroid Cells
Animals
Transcription Factors
Genes
Erythropoiesis
Essential Genes
Morphogenesis
Defects
Stem Cells
Mutation

ASJC Scopus subject areas

  • Cell Biology
  • Molecular Biology

Cite this

AML1, the target of multiple chromosomal translocations in human leukemia, is essential for normal fetal liver hematopoiesis. / Okuda, Tsukasa; Van Deursen, Jan; Hiebert, Scott W.; Grosveld, Gerard; Downing, James R.

In: Cell, Vol. 84, No. 2, 26.01.1996, p. 321-330.

Research output: Contribution to journalArticle

Okuda, Tsukasa ; Van Deursen, Jan ; Hiebert, Scott W. ; Grosveld, Gerard ; Downing, James R. / AML1, the target of multiple chromosomal translocations in human leukemia, is essential for normal fetal liver hematopoiesis. In: Cell. 1996 ; Vol. 84, No. 2. pp. 321-330.
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