University Of Tasmania

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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, RW
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.


Publication title

Cancer Cell








Menzies Institute for Medical Research


Cell Press

Place of publication

1100 Massachusetts Ave, Cambridge, USA, Ma, 02138

Rights statement

Crown Copyright 2016 Published by Elsevier Inc

Repository Status

  • Restricted

Socio-economic Objectives

Clinical health not elsewhere classified

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