Please use this identifier to cite or link to this item: https://doi.org/10.1038/s41467-018-03854-0
Title: The basic helix-loop-helix transcription factor SHARP1 is an oncogenic driver in MLL-AF6 acute myelogenous leukemia
Authors: Numata, Akihiko 
Kwok, Hui Si 
Kawasaki, Akira 
Li, Jia
Zhou, Qi-Ling 
Kerry, Jon
Benoukraf, Touati 
Bararia, Deepak 
Li, Feng 
Ballabio, Erica
Tapia, Marta
Deshpande, Aniruddha J
Welner, Robert S
Delwel, Ruud
Yang, Henry 
Milne, Thomas A
Taneja, Reshma 
Tenen, Daniel G 
Keywords: Science & Technology
Multidisciplinary Sciences
Science & Technology - Other Topics
ACUTE MYELOID-LEUKEMIA
MIXED-LINEAGE LEUKEMIA
STEM-CELLS
HISTONE METHYLTRANSFERASE
ACTIVE ENHANCERS
BINDING PROTEIN
GENE-EXPRESSION
TARGET GENES
DNA-DAMAGE
MLL
Issue Date: 24-Apr-2018
Publisher: NATURE PUBLISHING GROUP
Citation: Numata, Akihiko, Kwok, Hui Si, Kawasaki, Akira, Li, Jia, Zhou, Qi-Ling, Kerry, Jon, Benoukraf, Touati, Bararia, Deepak, Li, Feng, Ballabio, Erica, Tapia, Marta, Deshpande, Aniruddha J, Welner, Robert S, Delwel, Ruud, Yang, Henry, Milne, Thomas A, Taneja, Reshma, Tenen, Daniel G (2018-04-24). The basic helix-loop-helix transcription factor SHARP1 is an oncogenic driver in MLL-AF6 acute myelogenous leukemia. NATURE COMMUNICATIONS 9 (1). ScholarBank@NUS Repository. https://doi.org/10.1038/s41467-018-03854-0
Abstract: © 2018 The Author(s). Acute Myeloid Leukemia (AML) with MLL gene rearrangements demonstrate unique gene expression profiles driven by MLL-fusion proteins. Here, we identify the circadian clock transcription factor SHARP1 as a novel oncogenic target in MLL-AF6 AML, which has the worst prognosis among all subtypes of MLL-rearranged AMLs. SHARP1 is expressed solely in MLL-AF6 AML, and its expression is regulated directly by MLL-AF6/DOT1L. Suppression of SHARP1 induces robust apoptosis of human MLL-AF6 AML cells. Genetic deletion in mice delays the development of leukemia and attenuated leukemia-initiating potential, while sparing normal hematopoiesis. Mechanistically, SHARP1 binds to transcriptionally active chromatin across the genome and activates genes critical for cell survival as well as key oncogenic targets of MLL-AF6. Our findings demonstrate the unique oncogenic role for SHARP1 in MLL-AF6 AML.
Source Title: NATURE COMMUNICATIONS
URI: https://scholarbank.nus.edu.sg/handle/10635/155222
ISSN: 20411723
20411723
DOI: 10.1038/s41467-018-03854-0
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