| First Author | Saint Fleur-Lominy S | Year | 2018 |
| Journal | Cell Rep | Volume | 24 |
| Issue | 11 | Pages | 3045-3060.e5 |
| PubMed ID | 30208327 | Mgi Jnum | J:270937 |
| Mgi Id | MGI:6278345 | Doi | 10.1016/j.celrep.2018.08.030 |
| Citation | Saint Fleur-Lominy S, et al. (2018) STIM1 and STIM2 Mediate Cancer-Induced Inflammation in T Cell Acute Lymphoblastic Leukemia. Cell Rep 24(11):3045-3060.e5 |
| abstractText | T cell acute lymphoblastic leukemia (T-ALL) is commonly associated with activating mutations in the NOTCH1 pathway. Recent reports have shown a link between NOTCH1 signaling and intracellular Ca(2+) homeostasis in T-ALL. Here, we investigate the role of store-operated Ca(2+) entry (SOCE) mediated by the Ca(2+) channel ORAI1 and its activators STIM1 and STIM2 in T-ALL. Deletion of STIM1 and STIM2 in leukemic cells abolishes SOCE and significantly prolongs the survival of mice in a NOTCH1-dependent model of T-ALL. The survival advantage is unrelated to the leukemic cell burden but is associated with the SOCE-dependent ability of malignant T lymphoblasts to cause inflammation in leukemia-infiltrated organs. Mice with STIM1/STIM2-deficient T-ALL show a markedly reduced necroinflammatory response in leukemia-infiltrated organs and downregulation of signaling pathways previously linked to cancer-induced inflammation. Our study shows that leukemic T lymphoblasts cause inflammation of leukemia-infiltrated organs that is dependent on SOCE. |
