K-Ras is essential for normal fetal liver erythropoiesis

Waleed F. Khalaf, Hilary White, Mary Jo Wenning, Attilio Orazi, Reuben Kapur, David Ingram

Research output: Contribution to journalArticle

19 Citations (Scopus)

Abstract

In vitro studies suggest that Ras activation is necessary for erythroid cell development. However, genetic inactivation of the Ras isoforms H-Ras, N-Ras, and K-Ras in mice reportedly did not affect adult or fetal erythropoiesis, though K-Ras-/- embryos were anemic. Given these discrepancies, we performed a more detailed analysis of fetal erythropoiesis in K-Ras-/- embryos. Day-13.5 K-Ras-/- embryos were pale with a marked reduction of mature erythrocytes in their fetal livers. The frequency and number of both early (erythroid burst-forming unit [BFU-E]) and late erythroid progenitors (erythroid colony-forming unit [CFU-E]) were reduced in K-Ras-/- fetal livers compared with wild-type controls and displayed a delay in terminal erythroid cell maturation. Further, K-Ras-/- hematopoietic progenitors had reduced proliferation in response to erythropoietin and Kit ligand compared with control cells. Thus, these studies identify K-Ras as a unique Ras isoform that is essential for regulating fetal erythropoiesis in vivo.

Original languageEnglish
Pages (from-to)3538-3541
Number of pages4
JournalBlood
Volume105
Issue number9
DOIs
StatePublished - May 1 2005

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Erythroid Precursor Cells
Erythropoiesis
Liver
Protein Isoforms
Erythroid Cells
Stem Cell Factor
Embryonic Structures
Erythropoietin
Chemical activation
Erythrocytes

ASJC Scopus subject areas

  • Hematology

Cite this

K-Ras is essential for normal fetal liver erythropoiesis. / Khalaf, Waleed F.; White, Hilary; Wenning, Mary Jo; Orazi, Attilio; Kapur, Reuben; Ingram, David.

In: Blood, Vol. 105, No. 9, 01.05.2005, p. 3538-3541.

Research output: Contribution to journalArticle

Khalaf, WF, White, H, Wenning, MJ, Orazi, A, Kapur, R & Ingram, D 2005, 'K-Ras is essential for normal fetal liver erythropoiesis', Blood, vol. 105, no. 9, pp. 3538-3541. https://doi.org/10.1182/blood-2004-05-2021
Khalaf, Waleed F. ; White, Hilary ; Wenning, Mary Jo ; Orazi, Attilio ; Kapur, Reuben ; Ingram, David. / K-Ras is essential for normal fetal liver erythropoiesis. In: Blood. 2005 ; Vol. 105, No. 9. pp. 3538-3541.
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