Liberalis Debraj Boila, Subhadeep Ghosh, Subham K Bandyopadhyay, Liqing Jin, Alex Murison, Andy G X Zeng, Wasim Shaikh, Satyaki Bhowmik, Siva Sai Naga Anurag Muddineni, Mayukh Biswas, Sayantani Sinha, Shankha Subhra Chatterjee, Nathan Mbong, Olga I Gan, Anwesha Bose, Sayan Chakraborty, Andrea Arruda, James A Kennedy, Amanda Mitchell, Eric R Lechman, Debasis Banerjee, Michael Milyavsky, Mark D Minden, John E Dick, Amitava Sengupta
Acute myeloid leukemia (AML) is a heterogeneous, aggressive malignancy with dismal prognosis and with limited availability of targeted therapies. Epigenetic deregulation contributes to AML pathogenesis. KDM6 proteins are histone-3-lysine-27-demethylases that play context-dependent roles in AML. We inform that KDM6-demethylase function critically regulates DNA-damage-repair-(DDR) gene expression in AML. Mechanistically, KDM6 expression is regulated by genotoxic stress, with deficiency of KDM6A-(UTX) and KDM6B-(JMJD3) impairing DDR transcriptional activation and compromising repair potential...
April 2023: Leukemia