SETD2 alterations impair DNA damage recognition and lead to resistance to chemotherapy in leukemia

Brenton G. Mar(Dana-Farber Cancer Institute), S. Haihua Chu(Dana-Farber Cancer Institute), Josephine Kahn(Brigham and Women's Hospital), Andrei V. Krivtsov(Dana-Farber Cancer Institute), Richard P. Koche(Memorial Sloan Kettering Cancer Center), Cecilia A. Castellano(Brigham and Women's Hospital), Jacob L. Kotlier(Brigham and Women's Hospital), Rebecca L. Zon(Brigham and Women's Hospital), Marie McConkey(Brigham and Women's Hospital), Jonathan Chabon(Dana-Farber Cancer Institute), Ryan Chappell(Brigham and Women's Hospital), Peter Grauman(Brigham and Women's Hospital), James J. Hsieh(Washington University in St. Louis), Scott A. Armstrong(Dana-Farber Cancer Institute), Benjamin L. Ebert(Brigham and Women's Hospital)
Blood
October 11, 2017
Cited by 149Open Access
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Abstract

Key Points Alterations of SETD2, a histone 3 lysine 36 trimethyl (H3K36me3) transferase leads to resistance to DNA damaging-chemotherapy in leukemia. Low H3K36me3 levels impair DNA damage response and increase mutation rate, which may be targeted by H3K36me3 demethylase inhibition.


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