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Id2 and E proteins orchestrate the initiation and maintenance of MLL-rearranged acute myeloid leukemia
journal contribution
posted on 2023-05-20, 06:55 authored by Ghisi, M, Kats, L, Masson, F, Li, J, Kratina, T, Vidacs, E, Gilan, O, Doyle, MA, Newbold, A, Bolden, JE, Kirsten FairfaxKirsten Fairfax, de Graaf, CA, Firth, M, Zuber, J, Dickins, RA, Corcoran, LM, Dawson, MA, Belz, GT, Johnstone, RWE 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.
History
Publication title
Cancer CellVolume
30Pagination
59-74ISSN
1535-6108Department/School
Menzies Institute for Medical ResearchPublisher
Cell PressPlace of publication
1100 Massachusetts Ave, Cambridge, USA, Ma, 02138Rights statement
Crown Copyright 2016 Published by Elsevier IncRepository Status
- Restricted