A new correspondence published in Blood Research raises methodological concerns about a study claiming that targeting the HERV-K102 envelope (K-Env) triggers pyroptosis and offers a novel therapeutic strategy for acute myeloid leukemia. The original article by Zong and colleagues, published on 14 April 2026, reported that CRISPR-Cas9-mediated deletion of K-Env induces both apoptosis and pyroptosis in acute myeloid leukemia cells through activation of the S100A9/NLRP3 inflammasome pathway.
The correspondence, authored by Maajid Mohi Ud Din Malik and Rajesh Prasad Jayaswal, examines four specific methodological issues. First, the authors note the absence of evidence using a pathway-specific inhibitor to distinguish pyroptosis from secondary necrosis, a distinction they consider essential for interpreting the observed cell death. Second, they point to the lack of a mechanistic rescue experiment that would confirm S100A9 as the proximal driver of the reported cell death process.
Third, the correspondence argues that the primers used in the original study were non-specific at the mRNA level, raising questions about the molecular measurements underlying the proposed mechanism. Fourth, the authors highlight that the immunocompromised xenograft model employed in the study cannot capture immune evasion by K-Env, limiting what the in vivo findings can demonstrate about the protein’s role in the tumor microenvironment.
On the basis of these concerns, Malik and Jayaswal conclude that the prognostic and therapeutic implications of the original study require qualification. The correspondence is published as a Matters Arising item in open access form, appearing in Volume 61, article number 63 of Blood Research, dated 07 October 2026.
Subject of Research: Methodological critique of a study on HERV-K102 envelope targeting in acute myeloid leukemia
Article Title: Correspondence on: "Targeting the HERV-K102 envelope elicits pyroptosis and represents a novel therapeutic strategy for acute myeloid leukemia"
Article References: Malik, M. M. U. D., & Jayaswal, R. P. (2026). Correspondence on: "Targeting the HERV-K102 envelope elicits pyroptosis and represents a novel therapeutic strategy for acute myeloid leukemia". Blood Research, 61(1), Article 63. https://doi.org/10.1007/s44313-026-00151-4
Image Credits: AI Generated
DOI: 10.1007/s44313-026-00151-4
Keywords: HERV-K102, acute myeloid leukemia, pyroptosis, CRISPR-Cas9, S100A9, NLRP3 inflammasome, correspondence, Blood Research, xenograft model, methodology, Targeting, envelope
News Source: Nathaniel Bowman. (October 28, 2026). Scientists Challenge HERV-K102 Findings in Acute Myeloid Leukemia Study. Scienmag.



