@article{43c7e058ee4540f0ad6f09935f6b9583,
title = "The Oncogenic Transcription Factor RUNX1/ETO Corrupts Cell Cycle Regulation to Drive Leukemic Transformation: The Oncogenic Transcription Factor RUNX1/ETO Corrupts Cell Cycle Regulation to Drive Leukemic Transformation (Cancer Cell (2018) 34(4) (626–642.e8)(S1535610818303751)(10.1016/j.ccell.2018.08.015))",
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.",
keywords = "Animals, Cell Cycle Checkpoints/genetics, Cell Line, Tumor, Chromosomes, Human, Pair 21/genetics, Core Binding Factor Alpha 2 Subunit/genetics, Cyclin D2/genetics, Gene Expression Regulation, Leukemic/genetics, Humans, Leukemia, Myeloid, Acute/genetics, Male, Mice, Oncogene Proteins, Fusion/genetics, Oncogenes/genetics, Translocation, Genetic/genetics",
author = "Natalia Martinez-Soria and Lynsey McKenzie and Julia Draper and Anetta Ptasinska and Hasan Issa and Sandeep Potluri and Blair, {Helen J} and Anna Pickin and Asmida Isa and Chin, {Paulynn Suyin} and Ricky Tirtakusuma and Daniel Coleman and Sirintra Nakjang and Salam Assi and Victoria Forster and Mojgan Reza and Ed Law and Philip Berry and Dorothee Mueller and Cameron Osborne and Alex Elder and Bomken, {Simon N} and Deepali Pal and Allan, {James M} and Veal, {Gareth J} and Cockerill, {Peter N} and Christian Wichmann and Josef Vormoor and Georges Lacaud and Constanze Bonifer and Olaf Heidenreich",
note = "Copyright {\textcopyright} 2018 The Author(s). Published by Elsevier Inc. All rights reserved.",
year = "2018",
month = oct,
day = "8",
doi = "10.1016/j.ccell.2019.03.012",
language = "English",
volume = "34",
pages = "626--642.e8",
journal = "Cancer cell",
issn = "1535-6108",
publisher = "Cell Press",
number = "4",
}