T Acute Lymphoblastic Leukemia

Unexpectedly, increased editing levels in select genes ( CD247 , PRKCA and TRAF3IP2.ASI in T-ALL; SPPL3 in B-ALL) were significantly associated with better patient survival, suggesting a potential prognostic role for editing dysregulation at individual gene levels. Together, these results deepen our understanding of the pediatric ALL transcriptome landscape and provided novel candidate regulators and therapeutic targets for future mechanistic and translational investigation.

Notably, restoration of c-Myc effectively rescued T-ALL cells from the suppressive effects induced by ASS1 depletion. Collectively, our findings demonstrate that ASS1 supports mTORC1/c-Myc pathway activity by regulating arginine availability, thereby promoting the survival of T-ALL cells and leukemia progression.

P1, N=18, Recruiting, Peking University People's Hospital

Our work demonstrates that degradation of LMO2 affects T-ALL, and the lead compounds can eventually be developed into drugs for patient treatment. Our work describes methods for drug discovery starting with antibody fragments.

Bispecific antibodies such as blinatumomab (anti-CD19), antibody-drug conjugates like inotuzumab ozogamicin (anti-CD22), and monoclonal antibodies such as daratumumab (anti-CD38) have demonstrated efficacy in relapsed or refractory disease with improved safety profiles. The integration of targeted and immune-based therapies into conventional regimens represents a decisive step toward precision medicine, aiming to enhance survival outcomes while reducing treatment-related toxicity and improving quality of life in ALL children. This review aims to provide a comprehensive overview of the current understanding of ALL pathobiology and therapeutic approaches, with particular emphasis on the expanding role of immunotherapeutic strategies in pediatric disease.

Universal BE-CAR7 T cells induced leukemic remission in patients with relapsed or refractory T-cell ALL, thus allowing successful allogeneic hematopoietic stem-cell transplantation in most of the patients. (Funded by the Medical Research Council and others; ISRCTN Registry number, ISRCTN15323014.).

Collectively, these ncRNAs integrate into the complex regulatory circuits of KMT2A-r ALL, revealing their potential as biomarkers for disease classification, risk stratification, and treatment response prediction. Understanding their interplay with KMT2A fusion proteins not only provides new insights into leukemogenesis but also highlights promising opportunities for therapeutic intervention and precision medicine in this high-risk leukemia subtype.

Comparative analysis with idelalisib revealed similar toxicity profiles to Qona11, distinct from vincristine. In vivo studies in NOD/SCID mice bearing Jurkat xenografts showed that Qona11 (100 mg.kg-1) was well tolerated with no systemic toxicity, although it did not inhibit leukemia cell proliferation in immune-independent models. Overall, Qona11 exhibits promising anticancer activity and low systemic toxicity, warranting further preclinical investigation in solid tumor models and combination therapies.

P1, N=71, Active, not recruiting, City of Hope Medical Center | Trial completion date: Sep 2025 --> Jul 2026 | Trial primary completion date: Sep 2025 --> Jul 2026

P=N/A, N=10000, Recruiting, Goethe University | Trial completion date: Dec 2030 --> Dec 2035 | Trial primary completion date: Dec 2025 --> Dec 2030

Blinatumomab and inotuzumab ozogamicin have become established treatments, enhancing remission rates, measurable residual disease clearance, and overall survival in relapsed/refractory disease, and these agents, are now increasingly incorporated into frontline therapy...In acute myeloid leukemia (AML), gemtuzumab ozogamicin has shown significant clinical benefits, particularly in molecularly defined subsets...This review highlights how immunotherapy has reshaped treatment paradigms across acute leukemias, underscoring successful experiences in B-ALL. These insights emphasize the need for continued innovation to overcome existing hurdles in AML and T-ALL, ultimately aiming to enhance patient outcomes and quality of life.

Collectively, these advances highlight the potential of cellular therapies in high-risk leukemias and underscore the importance of continued innovation to improve outcomes in these historically treatment-refractory populations. Using a real-world case, we highlight the major challenges and innovative strategies shaping CAR T-cell therapy for T-cell acute lymphoblastic leukemia and acute myeloid leukemia.