| Literature DB >> 26859458 |
Ilaria Iacobucci1, Yongjin Li2, Kathryn G Roberts1, Stephanie M Dobson3, Jaeseung C Kim4, Debbie Payne-Turner1, Richard C Harvey5, Marcus Valentine6, Kelly McCastlain1, John Easton2, Donald Yergeau2, Laura J Janke1, Ying Shao7, I-Ming L Chen5, Michael Rusch2, Sasan Zandi3, Steven M Kornblau8, Marina Konopleva8, Elias Jabbour8, Elisabeth M Paietta9, Jacob M Rowe10, Ching-Hon Pui11, Julie Gastier-Foster12, Zhaohui Gu1, Shalini Reshmi12, Mignon L Loh13, Janis Racevskis8, Martin S Tallman14, Peter H Wiernik15, Mark R Litzow16, Cheryl L Willman5, John D McPherson17, James R Downing1, Jinghui Zhang2, John E Dick3, Stephen P Hunger18, Charles G Mullighan19.
Abstract
Chromosomal rearrangements are a hallmark of acute lymphoblastic leukemia (ALL) and are important ALL initiating events. We describe four different rearrangements of the erythropoietin receptor gene EPOR in Philadelphia chromosome-like (Ph-like) ALL. All of these rearrangements result in truncation of the cytoplasmic tail of EPOR at residues similar to those mutated in primary familial congenital polycythemia, with preservation of the proximal tyrosine essential for receptor activation and loss of distal regulatory residues. This resulted in deregulated EPOR expression, hypersensitivity to erythropoietin stimulation, and heightened JAK-STAT activation. Expression of truncated EPOR in mouse B cell progenitors induced ALL in vivo. Human leukemic cells with EPOR rearrangements were sensitive to JAK-STAT inhibition, suggesting a therapeutic option in high-risk ALL.Entities:
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Year: 2016 PMID： 26859458 PMCID： PMC4750652 DOI： 10.1016/j.ccell.2015.12.013
Source DB: PubMed Journal: Cancer Cell ISSN： 1535-6108 Impact factor: 31.743