Affiliation(s):
Department of Hematology, the Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou 310009, China;
moreAffiliation(s): Department of Hematology, the Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou 310009, China; Zhejiang Provincial Key Laboratory of Pancreatic Disease, The First Affiliated Hospital and Institute of Translational Medicine, Cancer Center, Zhejiang University School of Medicine, Hangzhou, Zhejiang 310029, China; Institute of Genetics, Zhejiang University and Department of Genetics, Zhejiang University School of Medicine, Hangzhou 310058, China; Division of Hematopoietic Stem Cell & Leukemia Research, Beckman Research Institute, City of Hope, Duarte, CA, 91010, USA; Department of Hematology, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200000, China;
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Liming LIN, Jingjing TAO, Ying MENG, Yichao GAN, Xin HE, Shu LI, Jiawei ZHANG, Feiqiong GAO, Dijia XIN, Luyao WANG, Yili FAN, Boxiao CHEN, Zhimin LU, Yang XU. Genome-wide CRISPR screening identifies critical role of PTEN in sensitivity of acute myeloid leukemia to chemotherapy[J]. Journal of Zhejiang University Science B,in press.Frontiers of Information Technology & Electronic Engineering,in press.https://doi.org/10.1631/jzus.B2300555
@article{title="Genome-wide CRISPR screening identifies critical role of PTEN in sensitivity of acute myeloid leukemia to chemotherapy", author="Liming LIN, Jingjing TAO, Ying MENG, Yichao GAN, Xin HE, Shu LI, Jiawei ZHANG, Feiqiong GAO, Dijia XIN, Luyao WANG, Yili FAN, Boxiao CHEN, Zhimin LU, Yang XU", journal="Journal of Zhejiang University Science B", year="in press", publisher="Zhejiang University Press & Springer", doi="https://doi.org/10.1631/jzus.B2300555" }
%0 Journal Article %T Genome-wide CRISPR screening identifies critical role of PTEN in sensitivity of acute myeloid leukemia to chemotherapy %A Liming LIN %A Jingjing TAO %A Ying MENG %A Yichao GAN %A Xin HE %A Shu LI %A Jiawei ZHANG %A Feiqiong GAO %A Dijia XIN %A Luyao WANG %A Yili FAN %A Boxiao CHEN %A Zhimin LU %A Yang XU %J Journal of Zhejiang University SCIENCE B %P %@ 1673-1581 %D in press %I Zhejiang University Press & Springer doi="https://doi.org/10.1631/jzus.B2300555"
TY - JOUR T1 - Genome-wide CRISPR screening identifies critical role of PTEN in sensitivity of acute myeloid leukemia to chemotherapy A1 - Liming LIN A1 - Jingjing TAO A1 - Ying MENG A1 - Yichao GAN A1 - Xin HE A1 - Shu LI A1 - Jiawei ZHANG A1 - Feiqiong GAO A1 - Dijia XIN A1 - Luyao WANG A1 - Yili FAN A1 - Boxiao CHEN A1 - Zhimin LU A1 - Yang XU J0 - Journal of Zhejiang University Science B SP - EP - %@ 1673-1581 Y1 - in press PB - Zhejiang University Press & Springer ER - doi="https://doi.org/10.1631/jzus.B2300555"
Abstract: Although significant progress has been made in the development of novel targeted drugs for the treatment of acute myeloid leukemia (AML) in recent years, chemotherapy still remains the mainstay of treatment and the overall survival is poor in most patients. Here, we demonstrated the antileukemia activity of a novel small molecular compound NL101, which is formed through the modification on bendamustine with a suberanilohydroxamic acid (SAHA) radical. NL101 suppresses the proliferation of myeloid malignancy cells and primary AML cells. It induces DNA damage and caspase 3-mediated apoptosis. A genome-wide clustered regularly interspaced short palindromic repeats (CRISPR) library screen revealed that PTEN gene is critical for the regulation of cell survival upon NL101 treatment. The knockout or inhibition of PTEN significantly reduced NL101-induced apoptosis in AML and MDS cells, accompanied by the activation of AKT signaling pathway. The inhibition of mTOR by rapamycin enhanced the sensitivity of AML cells to NL101-induced cell death. These findings uncover PTEN protein expression as a major determinant of chemosensitivity to NL101 and provide a novel strategy to treat AML with the combination of NL101 and rapamycin.
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