| First Author | Li J | Year | 2017 |
| Journal | Oncotarget | Volume | 8 |
| Issue | 5 | Pages | 8420-8435 |
| PubMed ID | 28039479 | Mgi Jnum | J:313232 |
| Mgi Id | MGI:6791732 | Doi | 10.18632/oncotarget.14220 |
| Citation | Li J, et al. (2017) Sensitizing leukemia stem cells to NF-kappaB inhibitor treatment in vivo by inactivation of both TNF and IL-1 signaling. Oncotarget 8(5):8420-8435 |
| abstractText | We previously reported that autocrine TNF-alpha (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-kappaB in AML stem cells (LSCs). In this study, we report that most TNF-expressing AML cells (LCs) also express another pro-inflammatory cytokine, IL1beta, which acts in a parallel manner. TNF was produced primarily by LSCs and leukemic progenitors (LPs), whereas IL1beta was mainly produced by partially differentiated leukemic blasts (LBs). IL1beta also stimulates an NF-kappaB-independent pro-survival and proliferation signal through activation of the JNK pathway. We determined that co-inhibition of signaling stimulated by both TNF and IL1beta synergizes with NF-kappaB 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. |
