Identification of TP53 germline variants in pediatric patients undergoing tumor testing: strategy and prevalence.

Background: TP53 alterations are common in certain pediatric cancers, making identification of putative germline variants through tumor genomic profiling crucial for disease management.

Methods: We analyzed TP53 alterations in 3123 tumors from 2788 pediatric patients sequenced using tumor-only or tumor-normal paired panels. Germline confirmatory testing was performed when indicated.

Condensate-Promoting ENL Mutation Drives Tumorigenesis In Vivo Through Dynamic Regulation of Histone Modifications and Gene Expression.

Gain-of-function mutations in the histone acetylation "reader" eleven-nineteen-leukemia (ENL), found in acute myeloid leukemia (AML) and Wilms tumor, are known to drive condensate formation and gene activation in cellular systems. However, their role in tumorigenesis remains unclear. Using a conditional knock-in mouse model, we show that mutant ENL perturbs normal hematopoiesis, induces aberrant expansion of myeloid progenitors, and triggers rapid onset of aggressive AML.

Reinfusion of CD19 CAR T cells for relapse prevention and treatment in children with acute lymphoblastic leukemia.

Relapse after CD19-directed chimeric antigen receptor (CAR)-modified T cells remains a substantial challenge. Short CAR T-cell persistence contributes to relapse risk, necessitating novel approaches to prolong durability. CAR T-cell reinfusion (CARTr) represents a potential strategy to reduce the risk of or treat relapsed disease after initial CAR T-cell infusion (CARTi).