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Role of Autophagy in Resistance of FLT3-ITD AML Stem Cells to FLT3 TKI Treatment

The FLT3-ITD mutation occurs in 25-30% of AML patients, and is associated with increased relapse rate and poor survival. FLT3 tyrosine kinase inhibitors (TKI) have shown encouraging results, but responses are not sustained. Therefore, there is considerable interest in understanding mechanisms of res...

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Bibliographic Details
Published in:Blood 2019-11, Vol.134 (Supplement_1), p.2548-2548
Main Authors: Qiu, Shaowei, Yan, Chengcheng, Paterson, Andrew J, Li, Hui, Anderson, Nick, Abraham, Ajay, He, Jianbo, Shah, Mansi, Agarwal, Puneet, Yang, Jing, Xie, Min, Lu, Rui, Welner, Rob S., Bhatia, Ravi
Format: Article
Language:English
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Summary:The FLT3-ITD mutation occurs in 25-30% of AML patients, and is associated with increased relapse rate and poor survival. FLT3 tyrosine kinase inhibitors (TKI) have shown encouraging results, but responses are not sustained. Therefore, there is considerable interest in understanding mechanisms of resistance of FLT3-ITD AML stem cells after TKI treatment. Autophagy is an important cellular response that maintains cell survival under stress. Here we investigated the regulation of autophagy in resistance of FLT3-ITD+ AML stem cells to FLT3 TKI treatment. MV4-11 and Molm13 FLT3-ITD AML cells were transduced with GFP-LC3-RFP-LC3 ΔG constructs to measure autophagic flux. Autophagyhigh AML cells showed slower growth(p
ISSN:0006-4971
1528-0020
DOI:10.1182/blood-2019-124948