Correspondence on: "Targeting the HERV-K102 envelope elicits pyroptosis and represents a novel therapeutic strategy for acute myeloid leukemia"

Zong et al. reported that CRISPR-Cas9-mediated deletion of the HERV-K102 envelope (K-Env) induces apoptosis and pyroptosis in acute myeloid leukemia cells via S100A9/NLRP3 inflammasome activation. We examine four methodological concerns: the absence of evidence using a pathway-specific inhibitor to distinguish pyroptosis from secondary necrosis; the lack of a mechanistic rescue experiment confirming S100A9 as the proximal driver; the non-specificity of primers at the mRNA level; and the inability of the immunocompromised xenograft model to capture immune evasion by K-Env. The prognostic and therapeutic implications of the study require qualification.