Activation of the cGAS/STING axis in genome-damaged hematopoietic cells doesnNot impact blood cell formation or leukemogenesis

Medientyp: E-Artikel

Titel: Activation of the cGAS/STING axis in genome-damaged hematopoietic cells doesnNot impact blood cell formation or leukemogenesis

Beteiligte: Dressel, Nicole [Verfasser:in]; Natusch, Loreen [Verfasser:in]; Munz, Clara M. [Verfasser:in]; Costas Ramon, Santiago [Verfasser:in]; Morcos, Mina [Verfasser:in]; Loff, Anja [Verfasser:in]; Hiller, Björn [Verfasser:in]; Haase, Christa [Verfasser:in]; Schulze, Livia [Verfasser:in]; Müller, Patrick [Verfasser:in]; Lesche, Mathias [Verfasser:in]; Dahl, Andreas [Verfasser:in]; Luksch, Hella [Verfasser:in]; Rösen-Wolff, Angela [Verfasser:in]; Roers, Axel [Verfasser:in]; Behrendt, Rayk [Verfasser:in]; Gerbaulet, Alexander [Verfasser:in]

Erschienen: 1 September 2023

Sprache: Englisch

DOI: 10.1158/0008-5472.CAN-22-3860

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Beschreibung: Genome damage is a main driver of malignant transformation, but it also induces aberrant inflammation via the cGAS/STING DNA-sensing pathway. Activation of cGAS/STING can trigger cell death and senescence, thereby potentially eliminating genome-damaged cells and preventing against malignant transformation. Here, we report that defective ribonucleotide excision repair (RER) in the hematopoietic system caused genome instability with concomitant activation of the cGAS/STING axis and compromised hematopoietic stem cell function, ultimately resulting in leukemogenesis. Additional inactivation of cGAS, STING, or type I IFN signaling, however, had no detectable effect on blood cell generation and leukemia development in RER-deficient hematopoietic cells. In wild-type mice, hematopoiesis under steady-state conditions and in response to genome damage was not affected by loss of cGAS. Together, these data challenge a role of the cGAS/STING pathway in protecting the hematopoietic system against DNA damage and leukemic transformation.Loss of cGAS/STING signaling does not impact DNA damage-driven leukemogenesis or alter steady-state, perturbed or malignant hematopoiesis, indicating that the cGAS/STING axis is not a crucial antioncogenic mechanism in the hematopoietic system.See related commentary by Zierhut, p. 2807

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