Extended Data Fig. 10: Proposed model – The stromal inflammasome maintains tissue equilibrium by restraining Ras activity to impede premalignant-to-malignant transition.

In the absence of inflammasome effectors caspases 1 and 11 in the bone marrow stroma, HSCs exhibited a distinct Ras-transduction signature associated with increased activity in the Ras pathway and an elevated expression of transcripts associated with cancer. Additionally, there was an increased presence of receptors for cytokines, chemokines, and growth-factors on HSCs. These findings suggest a model whereby inflammasome deficiency within the stroma creates a state of heightened Ras-dependent mitogenic processes, which cooperate with Myc upon its deregulation to accelerate the rate of malignant transformation and B cell lymphoma development. Created using BioRender.com and exported under a paid subscription to BioRender.