KDM6A promotes imatinib resistance through YY1-mediated transcriptional upregulation of TRKA independently of its demethylase activity in chronic myelogenous leukemia
Chengwan Zhang, Li Shen, Yifu Zhu, Ran Xu, Zhi-Kui Deng, Xiaoning Liu, Yihan Ding, Chunling Wang, Yuye Shi, Li-Ye Bei, Dongping Wei, Rick F. Thorne, Xu Dong Zhang, Liang Yu, Song Chen
Abstract
Contrary to its reported role as a tumor suppressor and independent of its demethylase function, KDM6A promotes imatinib-resistance in CML cells. The identification of the KDM6A/YY1/TRKA axis as a novel imatinib-resistance mechanism represents an unexplored avenue to overcome TKI resistance in CML.
Topics & Concepts
Chronic myelogenous leukemiaImatinibDownregulation and upregulationCancer researchLeukemiaDemethylaseChemistryMedicineImmunologyMyeloid leukemiaEpigeneticsGeneBiochemistryHistone Deacetylase Inhibitors ResearchCancer-related gene regulationProtein Degradation and Inhibitors