The oncogenic transcription factor RUNX1/ETO corrupts cell cycle regulation to drive leukemic transformation
Research output: Contribution to journal › Article › peer-review
Authors
Colleges, School and Institutes
Abstract
Oncogenic transcription factors such as the leukemic fusion protein RUNX1/ETO, which drives t(8;21) acute myeloid leukemia (AML), constitute cancer-specific but highly challenging therapeutic targets. We used epigenomic profiling data for an RNAi screen to interrogate the transcriptional network maintaining t(8;21) AML. This strategy identified Cyclin D2 (CCND2) as a crucial transmitter of RUNX1/ETO-driven leukemic propagation. RUNX1/ETO cooperates with AP-1 to drive CCND2 expression. Knockdown or pharmacological inhibition of CCND2 by an approved drug significantly impairs leukemic expansion of patient-derived AML cells and engraftment in immunodeficient murine hosts. Our data demonstrate that RUNX1/ETO maintains leukemia by promoting cell cycle progression and identifies G1 CCND-CDK complexes as promising therapeutic targets for treatment of RUNX1/ETO-driven AML.
Details
Original language | English |
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Pages (from-to) | 626-642.e8 |
Journal | Cancer Cell |
Volume | 34 |
Issue number | 4 |
Publication status | Published - 8 Oct 2018 |