Journal article
Id2 and E Proteins Orchestrate the Initiation and Maintenance of MLL-Rearranged Acute Myeloid Leukemia
M Ghisi, L Kats, F Masson, J Li, T Kratina, E Vidacs, O Gilan, MA Doyle, A Newbold, JE Bolden, KA Fairfax, CA de Graaf, M Firth, J Zuber, RA Dickins, LM Corcoran, MA Dawson, GT Belz, RW Johnstone
Cancer Cell | CELL PRESS | Published : 2016
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 signat..
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Awarded by Victorian Cancer Agency
Funding Acknowledgements
This work was funded by project and program grants (R.W.J.) from the National Health and Medical Research Council of Australia (NHMRC), a project grant from the Cancer Council Victoria (R.W.J.), the Victorian Cancer Agency (R.W.J.), Snowdome Foundation (R.W.J.), and an NHMRC Fellowship (R.W.J.). G.T.B. was supported by an NHMRC project grant (APP1047903) and an ARC Future fellowship. M.G. was supported by a Leukemia Foundation of Australia (LFA) Grant-in-Aid. M.A. Dawson was supported by the NHMRC, LFA, the Victorian Endowment for Science, Knowledge and Innovation (VESKI), and the Herman Trust. L.K., J.E.B., and C.A.d.G. were supported by Overseas-Based Biomedical Fellowships from the National Health and Medical Research Council of Australia. We thank Dr. P.J.M. Valk (Department of Hematology, Erasmus University Medical Center, Rotterdam, Netherlands) for providing clinical data associated to GSE6891 dataset and Prof. D. Hilton for sharing unpublished data.