Id2 and E proteins orchestrate the initiation and maintenance of MLL-rearranged acute myeloid leukemia

Ghisi, M; Kats, L; Masson, F; Li, J; Kratina, T; Vidacs, E; Gilan, O; Doyle, MA; Newbold, A; Bolden, JE; Fairfax, KA; de Graaf, CA; Firth, M; Zuber, J; Dickins, RA; Corcoran, LM; Dawson, MA; Belz, GT; Johnstone, RW

Author(s): Ghisi, M; Kats, L; Masson, F; Li, J; Kratina, T; Vidacs, E; Gilan, O; Doyle, MA; Newbold, A; Bolden, JE; Fairfax, KA; de Graaf, CA; Firth, M; Zuber, J; Dickins, RA; Corcoran, LM; Dawson, MA; Belz, GT; Johnstone, RW;
Details: Publication Year 2016-07-11,Volume 30,Issue #1,Page 59-74
Journal Title: Cancer Cell
Publication Type: Journal Article
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.
Publisher: Cell Press
Research Division(s): Molecular Immunology; Molecular Medicine
PubMed ID: 27374225
Publisher's Version: https://doi.org/10.1016/j.ccell.2016.05.019
Terms of Use/Rights Notice: Refer to copyright notice on published article.

Creation Date: 2016-08-10 04:12:52

Last Modified: 2016-08-11 09:55:31