T Acute Lymphoblastic Leukemia

This case highlights the diagnostic challenges of HLH in immunocompromised children, where early signs such as fever and cytopenias may be misattributed to sepsis or chemotherapy-related complications. It underscores the importance of including HLH in the differential diagnosis of ALF in high-risk patients and demonstrates that prompt recognition and targeted treatment of the hyperinflammatory state can be lifesaving, even in severe presentations.

P1, N=24, Recruiting, Ohio State University Comprehensive Cancer Center | Not yet recruiting --> Recruiting

At the molecular level, luteolin significantly downregulated the protein expression of p-PI3K, p-AKT, p-STAT3 and BCL-2, while upregulating the protein expression of BAX, cleaved caspase-3, and cleaved caspase-9. Luteolin may exert anti-Ph + ALL effects through the PI3K/AKT signaling pathway, accompanied by the regulation of other targets such as STAT3, which provides a theoretical basis for the development and screening of novel anti-Ph + ALL therapies.

7CAR also substantially impairs innate immunity by decreasing monocyte activation and eliminating dendritic cells, which may contribute to the high risk of infection. Thus, unlike CD19 and CD22 CAR therapy, which primarily affects B cells, 5CAR and 7CAR therapies result in broad dysregulation across multiple immune cell types, providing a basis for infection prevention and safer CAR-T therapy.

Furthermore, METTL13 was associated with a high-risk profile in pediatric T-cell acute lymphoblastic leukemia (T-ALL), and functional studies confirmed that METTL13 is required for T-ALL cell proliferation and survival both in vitro and in vivo. Collectively, our results indicate a previously unrecognized, oncogenic role for METTL13 in pre-leukemic transformation and T-ALL pathogenesis.

Based on in vitro kinetic and thermal shift assays, we find that ASX-173 binds to the ASNS/Mg 2+ /ATP complex and is therefore a rare example of an uncompetitive enzyme inhibitor with potential therapeutic use. These findings provide a structural and mechanistic basis for targeting ASNS with small molecules, which have application in treating cancer and other human diseases.

The present study demonstrates that a novel ATG4B-SESN3 regulatory circuit plays a crucial role in T cell leukemogenesis, which suggests that targeting ATG4B is a promising strategy for T-ALL treatment.

Inhibiting Rap1 signaling results in increased sensitivity to the BCL2/BCL-XL inhibitor navitoclax. Our study provides insights into the immune microenvironment of pediatric hematologic malignancies, forming the basis for identifying potential (immuno) therapeutic targets and risk stratification for treatment.

P1, N=66, Completed, National Cancer Institute (NCI) | Active, not recruiting --> Completed

MTAP rearrangement defines a distinct and clinically adverse subset of pediatric ALL characterized by specific fusion architecture and an unfavorable co-mutation pattern. Beyond its diagnostic value, MTAP-r represents a promising biomarker for trial enrollment and future risk-adapted strategies. Confirmation of independent prognostic impact and therapeutic utility will require multivariable analyses and prospective, biomarker-driven studies.

RT-qPCR analysis demonstrated downregulation of the Survivin gene, a key survival regulator. These findings highlight L-ASNase's potent antiproliferative, anti-migratory, and pro-apoptotic effects, underscoring its potential as an adjuvant therapy for GBM.