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LMO2 promotes the development of AML through interaction with transcription co-regulator LDB1

Authors :
Lihui Lu
Jianwei Wang
Fang Fang
Ailian Guo
Shuting Jiang
Yanfang Tao
Yongping Zhang
Yan Li
Kunlong Zhang
Zimu Zhang
Ran Zhuo
Xinran Chu
Xiaolu Li
Yuanyuan Tian
Li Ma
Xu Sang
Yanling Chen
Juanjuan Yu
Yang Yang
Haibo Cao
Jizhao Gao
Jun Lu
Shaoyan Hu
Jian Pan
Hailong He
Source :
Cell Death and Disease, Vol 14, Iss 8, Pp 1-15 (2023)
Publication Year :
2023
Publisher :
Nature Publishing Group, 2023.

Abstract

Abstract One of the characteristics of leukemia is that it contains multiple rearrangements of signal transduction genes and overexpression of non-mutant genes, such as transcription factors. As an important regulator of hematopoietic stem cell development and erythropoiesis, LMO2 is considered an effective carcinogenic driver in T cell lines and a marker of poor prognosis in patients with AML with normal karyotype. LDB1 is a key factor in the transformation of thymocytes into T-ALL induced by LMO2, and enhances the stability of carcinogenic related proteins in leukemia. However, the function and mechanism of LMO2 and LDB1 in AML remains unclear. Herein, the LMO2 gene was knocked down to observe its effects on proliferation, survival, and colony formation of NB4, Kasumi-1 and K562 cell lines. Using mass spectrometry and IP experiments, our results showed the presence of LMO2/LDB1 protein complex in AML cell lines, which is consistent with previous studies. Furthermore, in vitro and in vivo experiments revealed that LDB1 is essential for the proliferation and survival of AML cell lines. Analysis of RNA-seq and ChIP-Seq results showed that LDB1 could regulate apoptosis-related genes, including LMO2. In LDB1-deficient AML cell lines, the overexpression of LMO2 partially compensates for the proliferation inhibition. In summary, our findings revealed that LDB1 played an important role in AML as an oncogene, and emphasize the potential importance of the LMO2/LDB1 complex in clinical treatment of patients with AML.

Subjects

Subjects :
Cytology
QH573-671

Details

Language :
English
ISSN :
20414889
Volume :
14
Issue :
8
Database :
Directory of Open Access Journals
Journal :
Cell Death and Disease
Publication Type :
Academic Journal
Accession number :
edsdoj.8b32308fd0e34d84b5ed790e01293cad
Document Type :
article
Full Text :
https://doi.org/10.1038/s41419-023-06039-w