Crbn I391V is sufficient to confer in vivo sensitivity to thalidomide and its derivatives in mice

Emma C. Fink(Broad Institute), Marie McConkey(Broad Institute), Dylan N. Adams(Broad Institute), Saurav D. Haldar(Broad Institute), James A. Kennedy(Broad Institute), Andrew A. Guirguis(Broad Institute), Namrata D. Udeshi(Broad Institute), D.R. Mani(Broad Institute), Michelle Chen(Broad Institute), Brian Liddicoat(Broad Institute), Tanya Svinkina(Broad Institute), Andrew Nguyen(Broad Institute), Steven A. Carr(Broad Institute), Benjamin L. Ebert(Broad Institute)
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Abstract

Key Points Crbn I391V mice degrade known thalidomide derivative targets and recapitulate thalidomide-induced cytopenias and teratogenicity. Degradation of Ck1α is sufficient to explain the in vivo therapeutic window of lenalidomide in del(5q) myelodysplastic syndrome.


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