Somatic activation of a conditional KrasG12D allele causes ineffective erythropoiesis in vivo.
Somatic activation of a conditional targeted Kras(G12D) 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.
Braun
Benjamin S
BS
Department of Pediatrics, HSE-302, University of California-San Francisco, 513 Parnassus Avenue, San Francisco, CA 94143, USA.
Archard
Joehleen A
JA
Van Ziffle
Jessica A G
JA
Tuveson
David A
DA
Jacks
Tyler E
TE
Shannon
Kevin
K
D000483:Alleles; D000740:Anemia / Q000097:blood / Q000209:etiology / Q000235:genetics / Q000473:pathology; D000818:Animals; D004920:Erythropoiesis / Q000235:genetics*; D005786:Gene Expression Regulation; D011905:Genes, ras; D006801:Humans; D051379:Mice; D008810:Mice, Inbred C57BL; D008817:Mice, Mutant Strains; D009190:Myelodysplastic Syndromes / Q000235:genetics; D009196:Myeloproliferative Disorders / Q000235:genetics