CLC number:
On-line Access: 2024-08-27
Received: 2023-10-17
Revision Accepted: 2024-05-08
Crosschecked: 2024-08-19
Cited: 0
Clicked: 1050
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 phosphatase and tensin homologous (PTEN) in sensitivity of acute myeloid leukemia to chemotherapy[J]. Journal of Zhejiang University Science B, 2024, 25(8): 700-710.
@article{title="Genome-wide CRISPR screening identifies critical role of phosphatase and tensin homologous (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",
volume="25",
number="8",
pages="700-710",
year="2024",
publisher="Zhejiang University Press & Springer",
doi="10.1631/jzus.B2300555"
}
%0 Journal Article
%T Genome-wide CRISPR screening identifies critical role of phosphatase and tensin homologous (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
%V 25
%N 8
%P 700-710
%@ 1673-1581
%D 2024
%I Zhejiang University Press & Springer
%DOI 10.1631/jzus.B2300555
TY - JOUR
T1 - Genome-wide CRISPR screening identifies critical role of phosphatase and tensin homologous (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
VL - 25
IS - 8
SP - 700
EP - 710
%@ 1673-1581
Y1 - 2024
PB - Zhejiang University Press & Springer
ER -
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 phosphatase and tensin homologous (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 myelodysplastic syndrome (MDS) cells, accompanied by the activation of protein kinase B (AKT) signaling pathway. The inhibition of mammalian target of rapamycin (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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