Document Type
Article
Publication Date
2017
Publication Title
Oncotarget
Volume
8
Pages
8420-8435
Abstract
We previously reported that autocrine TNF-α (TNF) is responsible for JNK pathway activation in a subset of acute myeloid leukemia (AML) patient samples, providing a survival/proliferation signaling parallel to NF-κB in AML stem cells (LSCs). In this study, we report that most TNF-expressing AML cells (LCs) also express another pro-inflammatory cytokine, IL1β, which acts in a parallel manner. TNF was produced primarily by LSCs and leukemic progenitors (LPs), whereas IL1β was mainly produced by partially differentiated leukemic blasts (LBs). IL1β also stimulates an NF-κB-independent pro-survival and proliferation signal through activation of the JNK pathway. We determined that co-inhibition of signaling stimulated by both TNF and IL1β synergizes with NF-κB inhibition in eliminating LSCs both ex vivo and in vivo. Our studies show that such treatments are most effective in M4/5 subtypes of AML.
Recommended Citation
Breslin, Peter W.; Li, Jing; Volk, Andrew; Zhang, Jun; Cannova, Joseph; Dai, Shaojun; Hao, Caiqin; Hu, Chenglong; Sun, Jiewen; Xu, Yan; Wei, Wei; nand, Sucha; Chen, Jianjun; Kini, Ameet; Zhu, Jiang; and Zhang, Jiwang. Sensitizing Leukemia Stem Cells to NF-κB Inhibitor Treatment in Vivo by Inactivation of Both TNF and IL-1 Signaling. Oncotarget, 8, : 8420-8435, 2017. Retrieved from Loyola eCommons, Biology: Faculty Publications and Other Works, http://dx.doi.org/10.18632/oncotarget.14220
Creative Commons License
This work is licensed under a Creative Commons Attribution 4.0 International License.
Copyright Statement
© Jing Li, et al. 2017
Comments
Author Posting. © Jing Li, et al. 2017. This article is posted here by permission of Peter W. Breslin for personal use, not for redistribution. The article was published in Oncotarget, vol. 8, 2017, https://doi.org/10.18632/oncotarget.14220.