FGF18 mediates fibroblast-leukemia cross talk to promote acute myeloid leukemia progression.

Fibroblast-derived FGF18 promotes AML progression and immune suppression by activating FGFR3 signaling and forming a feed-forward loop in the bone marrow niche.

• Why it matters: Understanding stromal contributions to leukemia progression and immune evasion is crucial for developing targeted therapies, as their roles remain poorly defined in AML.
• What they did: The study used single-cell RNA sequencing, genetic depletion, and CRISPR-Cas9 screens to identify FGF18 and FGFR3 as key mediators, demonstrating that FGF18 accelerates AML via AKT-mTOR activation and IL-6 production.
• The result: Targeting FGF18 with a neutralizing antibody disrupted leukemia-stroma interactions, restored CD8+ T-cell function, and enhanced anti-PD-1 therapy, suggesting FGF18 neutralization as a promising treatment approach.