Loss of Runx1 perturbs adult hematopoiesis and is associated with a myeloproliferative phenotype

Joseph D. Growney, Hirokazu Shigematsu, Zhe Li, Benjamin H. Lee, Jennifer Adelsperger, Rebecca Rowan, David P. Curley, Jeffery L. Kutok, Koichi Akashi, Ifor R. Williams, Nancy A. Speck, D. Gary Gilliland

Research output: Contribution to journalArticle

310 Citations (Scopus)

Abstract

Homozygous loss of function of Runx1 (Runt-related transcription factor 1 gene) during murine development results in an embryonic lethal phenotype characterized by a complete lack of definitive hematopoiesis. In light of recent reports of disparate requirements for hematopoietic transcription factors during development as opposed to adult hematopoiesis, we used a conditional gene-targeting strategy to effect the loss of Runx1 function in adult mice. In contrast with the critical role of Runx1 during development, Runx1 was not essential for hematopoiesis in the adult hematopoietic compartment, though a number of significant hematopoietic abnormalities were observed. Runx1 excision had lineage-specific effects on B- and T-cell maturation and pronounced inhibition of common lymphocyte progenitor production. Runx1 excision also resulted in inefficient platelet production. Of note, Runx1-deficient mice developed a mild myeloproliferative phenotype characterized by an increase in peripheral blood neutrophils, an increase in myeloid progenitor populations, and extramedullary hematopoiesis composed of maturing myeloid and erythroid elements. These findings indicate that Runx1 deficiency has markedly different consequences during development compared with adult hematopoiesis, and they provide insight into the phenotypic manifestations of Runx1 deficiency in hematopoietic malignancies.

Original languageEnglish
Pages (from-to)494-504
Number of pages11
JournalBlood
Volume106
Issue number2
DOIs
Publication statusPublished - Jul 15 2005

    Fingerprint

All Science Journal Classification (ASJC) codes

  • Biochemistry
  • Immunology
  • Hematology
  • Cell Biology

Cite this

Growney, J. D., Shigematsu, H., Li, Z., Lee, B. H., Adelsperger, J., Rowan, R., ... Gilliland, D. G. (2005). Loss of Runx1 perturbs adult hematopoiesis and is associated with a myeloproliferative phenotype. Blood, 106(2), 494-504. https://doi.org/10.1182/blood-2004-08-3280