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

Citation

Ghisi, M and Kats, L and Masson, F and Li, J and Kratina, T and Vidacs, E and Gilan, O and Doyle, MA and Newbold, A and Bolden, JE and Fairfax, KA and de Graaf, CA and Firth, M and Zuber, J and Dickins, RA and Corcoran, LM and Dawson, MA and Belz, GT and Johnstone, RW, Id2 and E proteins orchestrate the initiation and maintenance of MLL-rearranged acute myeloid leukemia, Cancer Cell, 30, (1) pp. 59-74. ISSN 1535-6108 (2016) [Refereed Article]

Copyright Statement

Crown Copyright 2016 Published by Elsevier Inc

DOI: doi:10.1016/j.ccell.2016.05.019

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.

Item Details

Item Type:Refereed Article
Research Division:Biological Sciences
Research Group:Biochemistry and cell biology
Research Field:Cell development, proliferation and death
Objective Division:Health
Objective Group:Clinical health
Objective Field:Clinical health not elsewhere classified
UTAS Author:Fairfax, KA (Dr Kirsten Fairfax)
ID Code:134795
Year Published:2016
Web of Science® Times Cited:14
Deposited By:Menzies Institute for Medical Research
Deposited On:2019-09-05
Last Modified:2019-10-11
Downloads:0

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