T Acute Lymphoblastic Leukemia

The study demonstrated a high ratio of abnormal CD marker expression in AL cases, aligning previous data from various area around the world. Identifying aberrant antigen expression patterns through immunophenotyping aids in diagnosing leukemia and distinguishing neoplastic cells from normal hematopoietic precursors.

Despite this scientific and clinical progress, the high cost of developing CAR T cells through the traditional biopharma pathway is limiting late-stage clinical development, necessitating the creation of new business models to commercialize CAR T cells for these small markets. CAR T cells hold great promise for improving outcomes for pediatric patients with cancer, but substantial additional research and clinical development is needed if this promise is to be realized for children afflicted with cancer.

Functional assays demonstrate that QKI overexpression in T-ALL cells significantly reduces cell proliferation, induces G0/G1 cell cycle arrest, and limits leukemia progression and dissemination, ultimately improving survival in xenograft models. Together, these findings provide compelling evidence that QKI functions as a regulator of RNA splicing with tumor-suppressive activity in T-ALL.

P1, N=5, Terminated, Medical College of Wisconsin | N=24 --> 5 | Trial completion date: Jun 2026 --> Sep 2025 | Suspended --> Terminated; Low accrual

Space-time clustering at birth and diagnosis was observed in the HeH subgroup, suggesting potential etiologic heterogeneity in BCP-ALL. These findings support further investigation of environmental and infectious exposures across immunophenotypes and genetic subtypes in larger cohorts.

These findings couple histidine levels and translational control to cholesterol metabolism, which can be therapeutically exploited for cancer treatment. Our results suggest that defined dietary amino acid restrictions may expose broader therapeutic opportunities in diseases beyond cancer.

Furthermore, NKX2-1 positive cells showed less induction of DNA damage and apoptosis upon treatment with etoposide, a DNA damaging chemotherapy agent that is clinically used to treat T-ALL...Notably, NKX2-1 expressing cells showed higher sensitivity towards RUNX1 inhibition, suggesting a cooperative role in regulating T-ALL cell survival. This work reveals a critical role of NKX2-1 in enhancing T-ALL cell survival through DNA damage protection, and identifies RUNX1 as an important cofactor in T-ALL pathogenesis.

The combination of VEN and CDM exerts synergistic anti-leukemia effects by inhibiting cellular proliferation, inducing G0/G1 phase arrest and promoting apoptosis through PI3K/AKT/FoxO1 axis in T-ALL.

In contrast to treatment with mTORC1 inhibitors, these events culminate in robust and selective cell death in PTEN-deficient T-ALL cells. These findings reveal a targetable metabolic vulnerability in T-ALL, which could provide rationale for repurposing clinically approved IMPDH inhibitors.

In vivo experiments further confirmed that silencing SETD2 decreased the body weight of mice and increased the infiltration of JURKAT cells in the liver, kidney, spleen, lung, and brain, while overexpression of SETD2 showed inhibitory effects. In conclusion, SETD2 played an important role in T-ALL by inhibiting the JAK/STAT pathway to inhibit T-ALL proliferation, invasion, and transfection.

This study analyzed 24 R/R ALL patients receiving tisagenlecleucel after BT (Inotuzumab [n=10] vs. chemotherapy/steroids [n=14]). Overall, inotuzumab as BT effectively reduces tumor burden but attenuates CAR-T expansion without compromising survival outcomes. As high tumor burden is a dominant driver of relapse and toxicity, the net effect of inotuzumab may be favorable in selected patients.