TY  - JOUR
A1  - Saint Fleur-Lominy, Shella
A1  - Maus, Mate
A1  - Vaeth, Martin
A1  - Lange, Ingo
A1  - Zee, Isabelle
A1  - Suh, David
A1  - Liu, Cynthia
A1  - Wu, Xiaojun
A1  - Tikhonova, Anastasia
A1  - Aifantis, Iannis
A1  - Feske, Stefan
T1  - STIM1 and STIM2 Mediate Cancer-Induced Inflammation in T Cell Acute Lymphoblastic Leukemia
JF  - Cell Reports
N2  - 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 Ca2+ homeostasis in T-ALL. Here, we investigate the role of store-operated Ca2+ entry (SOCE) mediated by the Ca2+ 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.
KW  - T cell acute lymphoblastic leukemia
KW  - T-ALL
KW  - Notch1
KW  - STIM1
KW  - STIM2
KW  - calcium
KW  - Ca2+
KW  - CRAC
KW  - channel
KW  - inflammation
KW  - interferon
KW  - anemia
KW  - macrophages
Y1  - 2018
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-227259
VL  - 24
IS  - 11
ER  -