t(8;21) Acute Myeloid Leukaemia Requires Active CCND-CDK4/6

Introduction: The leukaemic fusion oncoprotein RUNX1/ETO, which results from the t(8;21) translocation, establishes a novel transcriptional programme maintaining leukaemia. Results: Functional interrogation of direct RUNX1/ETO target genes with an RNAi screen identified CCND2 as a crucial transmitter of RUNX1/ETO-driven maintenance of leukaemia both in tissue culture and in an NSG xenograft model. Knockdown of CCND2 caused a G1 cell cycle arrest and inhibited leukaemic proliferation and clonogenicity similarly to RUNX1/ETO knockdown. Since CCND2 forms a complex with the early G1 CDK4 and 6, we examined the impac…