Blood Podcast New Research: Mitochondrial DNA in TRALI and Venetoclax-Obinituzumab in CLL Trials
Nov 13, 2025
Join Dr. John Semple, a researcher at Lund University specializing in transfusion-related lung injuries, as he discusses how mitochondrial DNA acts as a critical trigger for TRALI via TLR9 signaling. Dr. Othman Al-Sawaf studies chronic lymphocytic leukemia and reveals surprising insights about patient fitness, highlighting that both fit and unfit patients respond similarly to treatment with venetoclax and obinutuzumab. Their research challenges existing views and suggests new pathways for understanding and treating these conditions.
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Mitochondrial DNA Triggers TRALI
- Mitochondrial DNA in aged platelet units can act as a potent first hit triggering TRALI in mice.
- Blocking TLR9 or antagonizing hypomethylated mtDNA prevents the TRALI response in the murine model.
TLR9 Is The Key Receptor
- Purified mitochondrial DNA and a synthetic CpG agonist (ODN 2395) acted as effective first hits before antibody challenge.
- A TLR9 antagonist (F448) completely blocked DNA-induced TRALI, implicating recipient TLR9 signaling.
Begin With In Vitro Assays
- Start with in vitro endothelial and neutrophil assays to test mtDNA effects before human studies.
- Use these assays to guide clinical study design because direct human TRALI experiments are challenging.