| Literature DB >> 27374225 |
Margherita Ghisi1, Lev Kats2, Frederick Masson3, Jason Li4, Tobias Kratina5, Eva Vidacs6, Omer Gilan2, Maria A Doyle7, Andrea Newbold2, Jessica E Bolden8, Kirsten A Fairfax8, Carolyn A de Graaf8, Matthew Firth5, Johannes Zuber9, Ross A Dickins10, Lynn M Corcoran5, Mark A Dawson2, Gabrielle T Belz5, Ricky W Johnstone11.
Abstract
E proteins and their antagonists, the Id proteins, are transcriptional regulators important for normal hematopoiesis. We found that Id2 acts as a key regulator of leukemia stem cell (LSC) potential in MLL-rearranged acute myeloid leukemia (AML). Low endogenous Id2 expression is associated with LSC enrichment while Id2 overexpression impairs MLL-AF9-leukemia initiation and growth. Importantly, MLL-AF9 itself controls the E-protein pathway by suppressing Id2 while directly activating E2-2 expression, and E2-2 depletion phenocopies Id2 overexpression in MLL-AF9-AML cells. Remarkably, Id2 tumor-suppressive function is conserved in t(8;21) AML. Low expression of Id2 and its associated gene signature are associated with poor prognosis in MLL-rearranged and t(8;21) AML patients, identifying the Id2/E-protein axis as a promising new therapeutic target in AML. CrownEntities:
Mesh：
Substances：
Year: 2016 PMID： 27374225 DOI： 10.1016/j.ccell.2016.05.019
Source DB: PubMed Journal: Cancer Cell ISSN： 1535-6108 Impact factor: 31.743