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阻断DNA损伤修复可能参与了Stattic（STAT3抑制剂）诱导的FLT3-ITD急性髓系白血病细胞凋亡。

Blocking DNA Damage Repair May Be Involved in Stattic (STAT3 Inhibitor)-Induced FLT3-ITD AML Cell Apoptosis.

作者信息

Luo Yuxuan, Lu Ying, Long Bing, Lin Yansi, Yang Yanling, Xu Yichuang, Zhang Xiangzhong, Zhang Jingwen

机构信息

Department of Pediatric, Guangzhou Women and Children's Medical Center, Guangzhou, China.

Department of Hematology, Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, China.

出版信息

Front Cell Dev Biol. 2021 Mar 16;9:637064. doi: 10.3389/fcell.2021.637064. eCollection 2021.

DOI:10.3389/fcell.2021.637064
PMID:33796529
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC8007876/
Abstract

The FMS-like tyrosine kinase 3 (FLT3)- internal tandem duplication (ITD) mutation can be found in approximately 25% of all acute myeloid leukemia (AML) cases and is associated with a poor prognosis. The main treatment for FLT3-ITD-positive AML patients includes genotoxic therapy and FLT3 inhibitors, which are rarely curative. Inhibiting STAT3 activity can improve the sensitivity of solid tumor cells to radiotherapy and chemotherapy. This study aimed to explore whether Stattic (a STAT3 inhibitor) affects FLT3-ITD AML cells and the underlying mechanism. Stattic can inhibit the proliferation, promote apoptosis, arrest cell cycle at G0/G1, and suppress DNA damage repair in MV4-11cells. During the process, through mRNA sequencing, we found that DNA damage repair-related mRNA are also altered during the process. In summary, the mechanism by which Stattic induces apoptosis in MV4-11cells may involve blocking DNA damage repair machineries.

摘要

在所有急性髓系白血病（AML）病例中，约25%可检测到FMS样酪氨酸激酶3（FLT3）内部串联重复（ITD）突变，该突变与预后不良相关。FLT3-ITD阳性AML患者的主要治疗方法包括基因毒性疗法和FLT3抑制剂，但这些方法很少能治愈疾病。抑制信号转导和转录激活因子3（STAT3）的活性可提高实体瘤细胞对放疗和化疗的敏感性。本研究旨在探讨Stattic（一种STAT3抑制剂）是否会影响FLT3-ITD AML细胞及其潜在机制。Stattic可抑制MV4-11细胞的增殖、促进其凋亡、使细胞周期停滞在G0/G1期，并抑制DNA损伤修复。在此过程中，通过mRNA测序，我们发现与DNA损伤修复相关的mRNA也发生了改变。总之，Stattic诱导MV4-11细胞凋亡的机制可能涉及阻断DNA损伤修复机制。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1bbb/8007876/efd71622f0ee/fcell-09-637064-g010.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1bbb/8007876/efd71622f0ee/fcell-09-637064-g010.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1bbb/8007876/4803d798bfff/fcell-09-637064-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1bbb/8007876/1a8dada3cfe1/fcell-09-637064-g007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1bbb/8007876/6d3dd8994b8e/fcell-09-637064-g008.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1bbb/8007876/efd71622f0ee/fcell-09-637064-g010.jpg

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