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Journal of Zhejiang University SCIENCE B 1998 Vol.-1 No.-1 P.

http://doi.org/10.1631/jzus.B2300555


Genome-wide CRISPR screening identifies critical role of PTEN in sensitivity of acute myeloid leukemia to chemotherapy


Author(s):  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

Affiliation(s):  Department of Hematology, the Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou 310009, China; more

Corresponding email(s):   zhiminlu@zju.edu.cn, yxu@zju.edu.cn

Key Words:  Genome-wide CRISPR library, PTEN, Rapamycin, AML, Chemotherapy


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, 1998, -1(-1): .

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%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
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%D 1998
%I Zhejiang University Press & Springer
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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
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PB - Zhejiang University Press & Springer
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DOI - 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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