Matches in SemOpenAlex for { <https://semopenalex.org/work/W2556142784> ?p ?o ?g. }
Showing items 1 to 82 of
82
with 100 items per page.
- W2556142784 abstract "Abstract Ras proteins modulate cell fates by integrating extracellular stimuli and transducing signals that regulate proliferation, survival, and differentiation via downstream effector cascades. Somatic activating mutations in RAS oncogenes are found in approximately one third of cases of myelodysplastic syndrome (MDS), and are common in myeloproliferative disorders (MPDs) such as CMML and JMML that frequently have a dysplastic component. We have modeled these human diseases in the mouse using a conditional allele of oncogenic Kras, which is activated in mice bearing the inducible Mx1-Cre transgene by injection with polyinosinic-polycytidilic acid (pI-pC). Mice treated with pI-pC to induce K-rasG12D expression at 21 days of life develop not only myeloid proliferation, but also progressive anemia which is the likely cause of death with median survival 84 days after injection. Erythroid precursors are abundant in spleens of anemic mice, suggesting ineffective erythropoiesis. These features are highly reminiscent of human MDS, and suggest that anemia in MDS is a direct consequence of hyperactive RAS signaling. Further analysis reveals that although erythroblasts are absent from the bone marrow, earlier erythroid progenitors such as BFU-E and CFU-E are abundant in both bone marrow and spleens of anemic mice. However, despite hyperproliferation of primitive erythroid cells, there is a block in terminal erythroid differentiation. This is also seen in primary E14.5 fetal liver cells acutely induced to express K-rasG12Din vitro, and in wild type recipients of Mx1-Cre, KrasG12D bone marrow, demonstrating this to be a cell-intrinsic property of erythroid progenitors expressing oncogenic Ras. Together, these findings support a model in which RAS mutations in MDS both confer a proliferative advantage to a neoplastic clone as well as directly impede differentiation, resulting in ineffective erythropoiesis and anemia. The improved efficiency of differentiation observed in spleen relative to bone marrow also suggests that microenvironmental influences modify the cell-intrinsic effects of oncogenic Ras." @default.
- W2556142784 created "2016-11-30" @default.
- W2556142784 creator A5011184671 @default.
- W2556142784 creator A5023734568 @default.
- W2556142784 creator A5024722625 @default.
- W2556142784 creator A5049938267 @default.
- W2556142784 creator A5071936673 @default.
- W2556142784 creator A5072185005 @default.
- W2556142784 date "2004-11-16" @default.
- W2556142784 modified "2023-09-28" @default.
- W2556142784 title "Anemia and Ineffective Erythropoiesis Caused by Somatic RAS Mutation." @default.
- W2556142784 doi "https://doi.org/10.1182/blood.v104.11.3419.3419" @default.
- W2556142784 hasPublicationYear "2004" @default.
- W2556142784 type Work @default.
- W2556142784 sameAs 2556142784 @default.
- W2556142784 citedByCount "0" @default.
- W2556142784 crossrefType "journal-article" @default.
- W2556142784 hasAuthorship W2556142784A5011184671 @default.
- W2556142784 hasAuthorship W2556142784A5023734568 @default.
- W2556142784 hasAuthorship W2556142784A5024722625 @default.
- W2556142784 hasAuthorship W2556142784A5049938267 @default.
- W2556142784 hasAuthorship W2556142784A5071936673 @default.
- W2556142784 hasAuthorship W2556142784A5072185005 @default.
- W2556142784 hasConcept C104317684 @default.
- W2556142784 hasConcept C109159458 @default.
- W2556142784 hasConcept C126322002 @default.
- W2556142784 hasConcept C134305767 @default.
- W2556142784 hasConcept C201750760 @default.
- W2556142784 hasConcept C203014093 @default.
- W2556142784 hasConcept C2778248108 @default.
- W2556142784 hasConcept C2778997081 @default.
- W2556142784 hasConcept C2779282312 @default.
- W2556142784 hasConcept C2779703530 @default.
- W2556142784 hasConcept C2780007613 @default.
- W2556142784 hasConcept C2780817109 @default.
- W2556142784 hasConcept C2780844101 @default.
- W2556142784 hasConcept C28328180 @default.
- W2556142784 hasConcept C502942594 @default.
- W2556142784 hasConcept C54355233 @default.
- W2556142784 hasConcept C67705224 @default.
- W2556142784 hasConcept C71924100 @default.
- W2556142784 hasConcept C86803240 @default.
- W2556142784 hasConcept C88478588 @default.
- W2556142784 hasConcept C95444343 @default.
- W2556142784 hasConceptScore W2556142784C104317684 @default.
- W2556142784 hasConceptScore W2556142784C109159458 @default.
- W2556142784 hasConceptScore W2556142784C126322002 @default.
- W2556142784 hasConceptScore W2556142784C134305767 @default.
- W2556142784 hasConceptScore W2556142784C201750760 @default.
- W2556142784 hasConceptScore W2556142784C203014093 @default.
- W2556142784 hasConceptScore W2556142784C2778248108 @default.
- W2556142784 hasConceptScore W2556142784C2778997081 @default.
- W2556142784 hasConceptScore W2556142784C2779282312 @default.
- W2556142784 hasConceptScore W2556142784C2779703530 @default.
- W2556142784 hasConceptScore W2556142784C2780007613 @default.
- W2556142784 hasConceptScore W2556142784C2780817109 @default.
- W2556142784 hasConceptScore W2556142784C2780844101 @default.
- W2556142784 hasConceptScore W2556142784C28328180 @default.
- W2556142784 hasConceptScore W2556142784C502942594 @default.
- W2556142784 hasConceptScore W2556142784C54355233 @default.
- W2556142784 hasConceptScore W2556142784C67705224 @default.
- W2556142784 hasConceptScore W2556142784C71924100 @default.
- W2556142784 hasConceptScore W2556142784C86803240 @default.
- W2556142784 hasConceptScore W2556142784C88478588 @default.
- W2556142784 hasConceptScore W2556142784C95444343 @default.
- W2556142784 hasLocation W25561427841 @default.
- W2556142784 hasOpenAccess W2556142784 @default.
- W2556142784 hasPrimaryLocation W25561427841 @default.
- W2556142784 hasRelatedWork W1969778053 @default.
- W2556142784 hasRelatedWork W1977841877 @default.
- W2556142784 hasRelatedWork W2008532188 @default.
- W2556142784 hasRelatedWork W2039817070 @default.
- W2556142784 hasRelatedWork W2092228026 @default.
- W2556142784 hasRelatedWork W2472644284 @default.
- W2556142784 hasRelatedWork W2516866347 @default.
- W2556142784 hasRelatedWork W2530984012 @default.
- W2556142784 hasRelatedWork W2556142784 @default.
- W2556142784 hasRelatedWork W4285507687 @default.
- W2556142784 isParatext "false" @default.
- W2556142784 isRetracted "false" @default.
- W2556142784 magId "2556142784" @default.
- W2556142784 workType "article" @default.