🔬 TP53 CLONAL HEMATOPOIESIS
Clinical Significance of TP53-Mutant Clonal Hematopoiesis Across Diseases (Blood Cancer Discovery, 2025) https://lnkd.in/da4bFD2J
10-year follow-up of 140,597 individuals in BioBank Japan assessing TP53-CHIP across cancers and systemic diseases.
TP53-CHIP is linked to reduced overall survival, especially in lymphoid, myeloid and respiratory diseases.
NOVELTY: TP53-CHIP significantly elevates mortality risk. Environmental factors (e.g., alcohol in myeloid neoplasms, smoking in respiratory diseases) further amplify this risk.
🧬 MYELOID NEOPLASIA
Efficacy of a novel BCL-xL degrader, DT2216, in preclinical models of JAK2-mutated post-MPN AML (Blood, 2025) https://lnkd.in/dEe8_KzF
JAK2-mutated post-MPN AML cells show a critical dependency on BCL-xL for survival.
DT2216, a selective BCL-xL degrader (PROTAC), demonstrated strong anti-leukemic activity in both preclinical models and patient-derived samples.
Combination with azacitidine, ruxolitinib, or venetoclax produced synergistic anti-tumor effects.
NOVELTY: DT2216 is a first-in-class BCL-xL-specific PROTAC that effectively targets a high-risk AML subset with limited treatment options.
🩸 SICKLE CELL THERAPIES
📜 Novel, potent, and orally bioavailable LSD1 inhibitors induce fetal hemoglobin synthesis in a sickle cell disease mouse model (Blood, 2025) https://lnkd.in/ddn5qAdK
➡️ New reversible LSD1 inhibitors increased fetal hemoglobin (HbF) and γ-globin in SCD mouse models, improving disease symptoms.
➡️ Combination with BRD4 degraders mitigated side effects commonly associated with LSD1 inhibition.
💡NOVELTY💡: Represents a promising therapeutic strategy to induce HbF in β-globinopathies while overcoming toxicity challenges of previous LSD1 inhibitors.
