Acute Myelogenous Leukemia

P=N/A, N=112, Completed, Bristol-Myers Squibb | Active, not recruiting --> Completed | Trial completion date: Oct 2024 --> Jan 2026 | Trial primary completion date: Oct 2024 --> Jan 2026

P1, N=21, Active, not recruiting, Senti Biosciences | Recruiting --> Active, not recruiting | Trial primary completion date: Sep 2025 --> Feb 2026

P=N/A, N=52, Recruiting, Centre Hospitalier Universitaire de Nice | Not yet recruiting --> Recruiting

Targeted therapies, such as tyrosine kinase inhibitors for Philadelphia chromosome-positive ALL, Chimeric Antigen Receptor T cell therapy for relapsed or refractory cases, and monoclonal antibodies like blinatumomab and inotuzumab ozogamicin, have transformed treatment outcomes while reducing chemotherapy-related toxicity. Despite these advances, challenges remain, including the development of therapy resistance (e.g., BCR-ABL1 and FLT3 mutations) and long-term adverse effects such as cardiotoxicity and secondary malignancies. This narrative review summarizes recent innovations in risk assessment and targeted therapies, highlights current challenges, and discusses future directions to optimize personalized pediatric leukemia care.

Several PROTAC therapies are now in AML trials. LSD1-targeted degradation is promising, but further research is needed to confirm its safety, overcome resistance, and identify optimal drug combinations for AML treatment.

Peptide-drug formulations containing the JAK2/FLT3 inhibitor lestaurtinib were investigated in acute myeloid leukemia models, resulting in enhanced anti-tumor efficacy. This work found that oligopeptides can be designed to efficiently co-assemble with therapeutic cargoes to result in high-loading nanoparticles that improve anti-tumor efficacy.

P1, N=2, Completed, Institute of Hematology & Blood Diseases Hospital, China | Not yet recruiting --> Completed | N=102 --> 2

P1/2, N=29, Recruiting, Institute of Hematology & Blood Diseases Hospital, China | Not yet recruiting --> Recruiting

We developed RMzyme, a platform that consolidates our findings and provides insights into RMPs and their downstream effects. This resource is expected to facilitate biomedical research into the molecular mechanisms of human diseases through the lens of RNA modifications and multiomics data integration.

Preclinical studies show that genetic depletion, small-molecule inhibition, or targeted degradation of FTO increases m6A on key targets, suppresses leukemic growth, and can sensitize cells to standard therapies, supporting FTO as a druggable epitranscriptomic vulnerability. This review summarizes FTO structure and function, highlights subtype-specific mechanisms in AML and ALL, and discusses emerging therapeutic strategies and translational challenges.

Further studies identified compound 1 as a type-I FLT3 inhibitor with comparable potency to quizartinib and gilteritinib; however, compound 1 is much more potent against MV4-11 cells, indicating that it may have a second molecular mechanism of action independent of FLT3 inhibition. Therefore, the high inhibitory potency of compound 1 on MV4-11 cells appear unlikely to be due to synergism of co-inhibition of FLT3 and any other kinases. Altogether, compound 1 may serve as a promising lead compound for further optimization and research on a potentially new molecular antiproliferative mechanism.