The non-cell-autonomous function of ID1 promotes AML progression via ANGPTL7 from the microenvironment.
The non-cell-autonomous function of ID1 promotes AML progression via ANGPTL7 from the microenvironment.
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DOI：
10.1182/blood.2022019537
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发表时间：
2023-09-07
期刊：
影响因子：
20.3
通讯作者：
Wang, Lan
中科院分区：
文献类型：
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作者：
Fei, Ming-Yue;Wang, Yong;Chang, Bin-He;Xue, Kai;Dong, Fangyi;Huang, Dan;Li, Xi-Ya;Li, Zi-Juan;Hu, Cheng-Long;Liu, Ping;Wu, Ji-Chuan;Yu, Peng-Cheng;Hong, Ming-Hua;Chen, Shu-Bei;Xu, Chun-Hui;Chen, Bing-Yi;Jiang, Yi-Lun;Liu, Na;Zhao, Chong;Jin, Jia-Cheng;Hou, Dan;Chen, Xin-Chi;Ren, Yi-Yi;Deng, Chu-Han;Zhang, Jia-Ying;Zong, Li-juan;Wang, Rou-Jia;Gao, Fei-Fei;Liu, Hui;Zhang, Qun-Ling;Wu, Ling-Yun;Yan, Jinsong;Shen, Shuhong;Chang, Chun-Kang;Sun, Xiao-Jian;Wang, Lan
ID1 deficiency in the AML BMM disrupts the progression of AML, which is restored by Angptl7. ID1 interacts with RNF4, attenuates SP1 ubiquitination, and contributes to the expression of ANGPTL7 in AML BM mesenchymal stem cells. The bone marrow microenvironment (BMM) can regulate leukemia stem cells (LSCs) via secreted factors. Increasing evidence suggests that dissecting the mechanisms by which the BMM maintains LSCs may lead to the development of effective therapies for the eradication of leukemia. Inhibitor of DNA binding 1 (ID1), a key transcriptional regulator in LSCs, previously identified by us, controls cytokine production in the BMM, but the role of ID1 in acute myeloid leukemia (AML) BMM remains obscure. Here, we report that ID1 is highly expressed in the BMM of patients with AML, especially in BM mesenchymal stem cells, and that the high expression of ID1 in the AML BMM is induced by BMP6, secreted from AML cells. Knocking out ID1 in mesenchymal cells significantly suppresses the proliferation of cocultured AML cells. Loss of Id1 in the BMM results in impaired AML progression in AML mouse models. Mechanistically, we found that Id1 deficiency significantly reduces SP1 protein levels in mesenchymal cells cocultured with AML cells. Using ID1-interactome analysis, we found that ID1 interacts with RNF4, an E3 ubiquitin ligase, and causes a decrease in SP1 ubiquitination. Disrupting the ID1-RNF4 interaction via truncation in mesenchymal cells significantly reduces SP1 protein levels and delays AML cell proliferation. We identify that the target of Sp1, Angptl7, is the primary differentially expression protein factor in Id1-deficient BM supernatant fluid to regulate AML progression in mice. Our study highlights the critical role of ID1 in the AML BMM and aids the development of therapeutic strategies for AML. Inhibitor of DNA binding 1 (ID1) is a transcriptional regulator found in normal and acute myeloid leukemia (AML) stem cells that controls cytokine production in the bone marrow microenvironment (BMM). In a mechanistic study using primary patient samples and murine models, Fei et al identified a regulatory loop in which specific leukemogenic fusion proteins increase BMP6 expression that is then secreted into the BMM, where it upregulates ID1 in mesenchymal stromal cells and increases angiopoietin-like 7 (ANGPTL7) production, which in turn promotes leukemia growth in vitro and in vivo. These findings point to ID1 and the ANGPTL7 axis as therapeutic targets in AML.
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影响因子：
8.8
作者：
Gadomski S;Singh SK;Singh S;Sarkar T;Klarmann KD;Berenschot M;Seaman S;Jakubison B;Gudmundsson KO;Lockett S;Keller JR
通讯作者：
Keller JR
影响因子：
44.1
作者：
Hu, Cheng-Long;Chen, Bing-Yi;Li, Zijuan;Yang, Tianbiao;Xu, Chun-Hui;Yang, Ruirui;Yu, Peng-Cheng;Zhao, Jingyao;Liu, Ting;Liu, Na;Shan, Bin;Zhang, Qunling;Song, Junhong;Fei, Ming-Yue;Zong, Li-Juan;Zhang, Jia-Ying;Wu, Ji-Chuan;Chen, Shu-Bei;Wang, Yong;Chang, Binhe;Hou, Dan;Liu, Ping;Jiang, Yilun;Li, Xiya;Chen, Xinchi;Deng, Chu-Han;Ren, Yi-Yi;Wang, Roujia;Jin, Jiacheng;Xue, Kai;Zhang, Ying;Du, Meirong;Shi, Jun;Wu, Ling-Yun;Chang, Chun-Kang;Shen, Shuhong;Chen, Zhu;Chen, Sai-Juan;Liu, Xiaolong;Sun, Xiao-Jian;Zheng, Mingyue;Wang, Lan
通讯作者：
Wang, Lan
影响因子：
11.4
作者：
Dar, A.;Schajnovitz, A.;Lapid, K.;Kalinkovich, A.;Itkin, T.;Ludin, A.;Kao, W-M;Battista, M.;Tesio, M.;Kollet, O.;Cohen, N. N.;Margalit, R.;Buss, E. C.;Baleux, F.;Oishi, S.;Fujii, N.;Larochelle, A.;Dunbar, C. E.;Broxmeyer, H. E.;Frenette, P. S.;Lapidot, T.
通讯作者：
Lapidot, T.
影响因子：
82.9
作者：
Li S;Garrett-Bakelman FE;Chung SS;Sanders MA;Hricik T;Rapaport F;Patel J;Dillon R;Vijay P;Brown AL;Perl AE;Cannon J;Bullinger L;Luger S;Becker M;Lewis ID;To LB;Delwel R;Löwenberg B;Döhner H;Döhner K;Guzman ML;Hassane DC;Roboz GJ;Grimwade D;Valk PJ;D'Andrea RJ;Carroll M;Park CY;Neuberg D;Levine R;Melnick AM;Mason CE
通讯作者：
Mason CE
影响因子：
82.9
作者：
通讯作者：
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