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Oncogenic transcription factors such as the leukaemic fusion protein RUNX1/ETO, which drives t(8;21) acute myeloid leukaemia (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 leukaemic propagation. RUNX1/ETO cooperates with AP-1 to drive CCND2 expression. Knockdown or pharmacological inhibition of CCND2 by an approved drug significantly impairs leukaemic expansion of patient-derived AML cells and engraftment in immunodeficient murine hosts. Our data demonstrate that RUNX1/ETO maintains leukaemia by promoting cell cycle progression and identifies G1 CCND-CDK complexes as promising therapeutic targets for treatment of RUNX1/ETO-driven AML.
Oncogenic transcription factors such as the leukaemic fusion protein RUNX1/ETO, which drives t(8;21) acute myeloid leukaemia (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 leukaemic propagation. RUNX1/ETO cooperates with AP-1 to drive CCND2 expression. Knockdown or pharmacological inhibition of CCND2 by an approved drug significantly impairs leukaemic expansion of patient-derived AML cells and engraftment in immunodeficient murine hosts. Our data demonstrate that RUNX1/ETO maintains leukaemia by promoting cell cycle progression and identifies G1 CCND-CDK complexes as promising therapeutic targets for treatment of RUNX1/ETO-driven AML.
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Senior Group Leader
“It is a pleasure to introduce my team who work to deliver our research goals. We work in a friendly and collaborative environment, supporting each other’s projects. “
Amaya Virós
CRUK Advanced Clinician Scientist Fellow
“We are so pleased to have received the funding to enable us to test our hypothesis in the lab. If we can create a new medicine that can precisely target a specific type of cell within the tumour, and restore anti-cancer immune responses, this will be a game-changer for oesophageal cancer patients “
Sara Valpione
Former Institute Clinical Fellow and now Clinician in Residence within the CRUK National Biomarker Centre
“My charity bake sales – known as “David’s Great British Bake Off” – are always a hit, home baked products taste so much better than shop bought and are greatly appreciated by staff!”
David Jenkins
Purchasing Officer
“We’ve seen some remarkable responses, with an improvement for some patients within days. This is an early phase trial so there’s a lot more work to do. But the data we have so far is very encouraging and could help many thousands of people in the future”
Tim Somervaille
Senior Group Leader
“It is a pleasure to introduce my team who work to deliver our research goals. We work in a friendly and collaborative environment, supporting each other’s projects. “
Amaya Virós
CRUK Advanced Clinician Scientist Fellow