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 Blood, 15 September 2006, Vol. 108, No. 6, pp. 2041-2044.
Prepublished online as a Blood First Edition Paper on May 23, 2006; DOI 10.1182/blood-2006-01-013490.

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NEOPLASIA
Brief report

Somatic activation of a conditional KrasG12D allele causes ineffective erythropoiesis in vivo

Benjamin S. Braun, Joehleen A. Archard, Jessica A. G. Van Ziffle, David A. Tuveson, Tyler E. Jacks, and Kevin Shannon

From the Department of Pediatrics, University of California, San Francisco (UCSF), San Francisco, CA; Department of Medicine, University of Pennsylvania, Philadelphia, PA; and Department of Biology, Massachusetts Institute of Technology, Cambridge, MA.

Somatic activation of a conditional targeted KrasG12D allele induces a fatal myeloproliferative disease in mice that closely models juvenile and chronic myelomonocytic leukemia. These mice consistently develop severe and progressive anemia despite adequate numbers of clonogenic erythroid progenitors in the bone marrow and expanded splenic hematopoiesis. Ineffective erythropoiesis is characterized by impaired differentiation. These results demonstrate that endogenous levels of oncogenic Ras have cell lineage-specific effects and support efforts to modulate Ras signaling for therapy of anemia in patients with myelodysplastic syndromes and myeloproliferative disorders.


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