Blood Podcast A key role for T-cell TET3 in chronic GVHD; a BTK inhibitor for ITP; co-inhibition of pre-TCR and IL-7R pathways in a T-ALL patient subset
Jun 12, 2025
Discover the pivotal role of TET3 in chronic GVHD and its potential as a therapeutic target to combat lung fibrosis. Learn about the promising results of rilzabrutinib, a BTK inhibitor, showing significant platelet responses for those suffering from immune thrombocytopenia. Finally, dive into the complexities of T-cell acute lymphoblastic leukemia and how co-inhibition strategies for pre-TCR and IL-7 pathways may open new avenues for treatment. It's a compelling look into groundbreaking research and innovative approaches in hematology.
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TET3's Role in Chronic GVHD
- TET3 in donor T-follicular helper cells is crucial for inducing pathogenic IgG2C class switching causing chronic GVHD lung fibrosis.
- Loss of TET3 shifts class switching to non-pathogenic IgG1, reducing lung fibrosis and improving pulmonary function in mouse models.
Rilzabrutinib's Success in ITP
- Rilzabrutinib, a BTK inhibitor, produces rapid and durable platelet responses in adults with chronic ITP who failed multiple therapies.
- Treatment also improves quality of life and fatigue with a favorable safety profile in a randomized Phase 3 trial.
Pre-TCR and IL-7R Dual Targeting in T-ALL
- Surface pre-TCR (PT-alpha) expression identifies a subset of cortical T-ALL with activated LCK kinase signaling.
- Dual inhibition of pre-TCR (LCK) and IL-7R (JAK) pathways shows synergistic cytotoxicity preclinically, offering a precision therapeutic approach.