STIM1 and STIM2 Mediate Cancer-Induced Inflammation in T Cell Acute Lymphoblastic Leukemia

Shella Saint Fleur-Lominy, Mate Maus, Martin Vaeth, Ingo Lange, Isabelle Zee, David Suh, Cynthia Liu, Xiaojun Wu, Anastasia Tikhonova, Iannis Aifantis, Stefan Feske

Research output: Contribution to journalArticle

Abstract

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. T cell acute lymphoblastic leukemia (T-ALL) is an aggressive cancer of T cell progenitors affecting children and adults. Saint Fleur-Lominy et al. show that calcium influx mediated by STIM1 and STIM2 promotes the proinflammatory function of leukemic cells and premature death from leukemia.

Original languageEnglish (US)
Pages (from-to)3045-3060.e5
JournalCell Reports
Volume24
Issue number11
DOIs
StatePublished - Sep 11 2018

Fingerprint

Precursor T-Cell Lymphoblastic Leukemia-Lymphoma
T-cells
Inflammation
Leukemia
Neoplasms
Premature Mortality
Homeostasis
Cell Death
Down-Regulation
Calcium
T-Lymphocytes
Mutation

Keywords

  • anemia
  • Ca
  • calcium
  • CRAC channel
  • inflammation
  • interferon
  • macrophages
  • Notch1
  • STIM1
  • STIM2
  • T cell acute lymphoblastic leukemia
  • T-ALL

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)

Cite this

Saint Fleur-Lominy, S., Maus, M., Vaeth, M., Lange, I., Zee, I., Suh, D., ... Feske, S. (2018). STIM1 and STIM2 Mediate Cancer-Induced Inflammation in T Cell Acute Lymphoblastic Leukemia. Cell Reports, 24(11), 3045-3060.e5. https://doi.org/10.1016/j.celrep.2018.08.030

STIM1 and STIM2 Mediate Cancer-Induced Inflammation in T Cell Acute Lymphoblastic Leukemia. / Saint Fleur-Lominy, Shella; Maus, Mate; Vaeth, Martin; Lange, Ingo; Zee, Isabelle; Suh, David; Liu, Cynthia; Wu, Xiaojun; Tikhonova, Anastasia; Aifantis, Iannis; Feske, Stefan.

In: Cell Reports, Vol. 24, No. 11, 11.09.2018, p. 3045-3060.e5.

Research output: Contribution to journalArticle

Saint Fleur-Lominy, S, Maus, M, Vaeth, M, Lange, I, Zee, I, Suh, D, Liu, C, Wu, X, Tikhonova, A, Aifantis, I & Feske, S 2018, 'STIM1 and STIM2 Mediate Cancer-Induced Inflammation in T Cell Acute Lymphoblastic Leukemia', Cell Reports, vol. 24, no. 11, pp. 3045-3060.e5. https://doi.org/10.1016/j.celrep.2018.08.030
Saint Fleur-Lominy S, Maus M, Vaeth M, Lange I, Zee I, Suh D et al. STIM1 and STIM2 Mediate Cancer-Induced Inflammation in T Cell Acute Lymphoblastic Leukemia. Cell Reports. 2018 Sep 11;24(11):3045-3060.e5. https://doi.org/10.1016/j.celrep.2018.08.030
Saint Fleur-Lominy, Shella ; Maus, Mate ; Vaeth, Martin ; Lange, Ingo ; Zee, Isabelle ; Suh, David ; Liu, Cynthia ; Wu, Xiaojun ; Tikhonova, Anastasia ; Aifantis, Iannis ; Feske, Stefan. / STIM1 and STIM2 Mediate Cancer-Induced Inflammation in T Cell Acute Lymphoblastic Leukemia. In: Cell Reports. 2018 ; Vol. 24, No. 11. pp. 3045-3060.e5.
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AU - Vaeth, Martin

AU - Lange, Ingo

AU - Zee, Isabelle

AU - Suh, David

AU - Liu, Cynthia

AU - Wu, Xiaojun

AU - Tikhonova, Anastasia

AU - Aifantis, Iannis

AU - Feske, Stefan

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