biostudies-literature00400Braun BSNCI NIH HHS2041-4https://www.ebi.ac.uk/biostudies/studies/S-EPMC1895533biostudies-literatureUnknown108(6)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.BloodSomatic activation of a conditional KrasG12D allele causes ineffective erythropoiesis in vivo.PMC1895533K08 CA 103868R01 CA 72614P30 CA 082103Tuveson DAJacks TEVan Ziffle JABraun BSShannon KArchard JA40falseSomatic 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.2006-01-01T00:00:00Z2006 Sep2024-11-05T19:57:18.635Z2019-03-27T02:04:10ZS-EPMC18955331672083710.1182/blood-2006-01-013490