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Targeting IFN-γ-inducible lysosomal thiol reductase Overcomes Chemoresistance in AML through Regulating the ROS-mediated mitochondrial damage

ABSTRACT: Our work demonstrated that the inhibition of GILT increases AML chemo-sensitivity through elevating ROS level and induce oxidative mitochondrial damage-mediated apoptosis, and inhibition of the PI3K/Akt/NRF2 pathway enhances the intracellular oxidative state by disrupting redox homeostasis. Our study provides a potentially effective way to overcome chemoresistance of AML.

ORGANISM(S): Homo Sapiens

SUBMITTER: Xiao-Jun Huang

PROVIDER: PXD025114 | iProX | Wed Mar 31 00:00:00 GMT+01:00 2021

REPOSITORIES: iProX

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Targeting IFN-γ-inducible lysosomal thiol reductase overcomes chemoresistance in AML through regulating the ROS-mediated mitochondrial damage.

Niu Li-Ting LT Wang Yu-Qing YQ Wong Catherine C L CCL Gao Shuai-Xin SX Mo Xiao-Dong XD Huang Xiao-Jun XJ

Translational oncology 20210709 9

The persistence of leukemia stem cells (LSCs) is one of the leading causes of chemoresistance in acute myeloid leukemia (AML). To explore the factors important in LSC-mediated resistance, we use mass spectrometry to screen the factors related to LSC chemoresistance and defined IFN-γ-inducible lysosomal thiol reductase (GILT) as a candidate. We found that the GILT expression was upregulated in chemoresistant CD34+ AML cells. Loss of function studies demonstrated that silencing of GILT in AML cell ...[more]

PMID: 34252711

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