Blood Podcast “Ironing out” Tet2-mutant HSPCs; A CAR-T “license to kill” in T cell leukemia/lymphoma; insights on cHL genetics, through the lens of ctDNA
Sep 4, 2025
Discover how mutations in TET2 influence myeloid malignancies and the role of NCOA4 in supporting Tet2-deficient cells. Dive into the promising results from a groundbreaking CAR T therapy that could offer hope for patients with T-cell leukemia and lymphoma. Lastly, explore new insights from a comprehensive study on classical Hodgkin lymphoma genetics through circulating tumor DNA, revealing key subtypes and prognostic markers. These topics promise to reshape our understanding of blood cancers.
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Ferritinophagy Fuels TET2-Mutant HSC Expansion
- TET2-deficient HSPCs rely on NCOA4-mediated ferritinophagy to supply labile iron for increased mitochondrial ATP production.
- Blocking ferritinophagy genetically or with ironomycin selectively impairs TET2-mutant clonal expansion without harming wild-type HSPCs.
Barcoded In Vivo CRISPR Reveals Hidden Dependencies
- A barcoded in vivo lentiviral CRISPR-Cas9 screen lets researchers induce gene perturbations and clonally track long-term HSPC growth using unique molecular identifiers.
- This approach reveals late clonal dependencies that standard screens might miss due to HSPC heterogeneity.
Target Ferritinophagy As A Therapeutic Strategy
- Target ferritinophagy to potentially prevent or delay malignant progression in TET2-mutant clonal hematopoiesis.
- Consider agents like ironomycin or NCOA4 inhibition as selective strategies that spare wild-type HSPCs.