Id2 and E proteins orchestrate the initiation and maintenance of MLL-rearranged acute myeloid leukemia
Publication Year 2016-07-11, Volume 30, Issue #1, Page 59-74
Journal Title
Cancer Cell
Publication Type
Journal Article
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.
Cell Press
WEHI Research Division(s)
Molecular Immunology; Molecular Medicine
PubMed ID
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Creation Date: 2016-08-10 04:12:52
Last Modified: 2016-08-11 09:55:31
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