KMT2A (Lysine Methyltransferase 2A)

In most dual-driver cases, one subtype gene expression signature predominated, consistent with oncogenic hierarchies, but also with the possibility of technical artifacts, which should prompt individual orthogonal validations. IntegrateALL provides an adaptable fully reproducible workflow for molecular B-ALL characterization by systematically integrating genomic drivers and downstream gene regulation.

He was initially treated with azacitidine and venetoclax but demonstrated disease progression. In the setting of a KMT2A::ELL fusion, therapy was transitioned to the menin inhibitor revumenib, resulting in short-term clinical stability and tolerability under continued supportive care.

The cells still exhibited high lineage plasticity, switching from a myeloid to a B-lymphoid identity in vivo. In conclusion, this model enables the mechanistic dissection of MLL fusion variants in vitro and in vivo, providing a foundation for developing targeted therapies for MLL-rearranged leukemias.

Key advancements include the integration of FLT3 inhibitors into intensive chemotherapy and the emergence of venetoclax...Innovations such as the liposomal formulation CPX-351 and oral formulations of CC-486 and oral decitabine/cedazuridine have further optimized treatment delivery and improved patient quality of life...Current research is actively exploring next-generation inhibitors, antibody-drug conjugates, and cellular immunotherapies such as BiTEs and CAR-T cells. This review summarizes the recent pharmacological evolution in AML and discusses how these emerging therapies bring us closer to the ultimate goal of achieving a definitive cure.

P2/3, N=25, Recruiting, Medical University Of Lodz | Not yet recruiting --> Recruiting

Mechanistically, PTP4A2 directly interacts with p53 and dephosphorylates it at serine 392, decreasing p53 stability and activity to enhance LIC proliferation and survival. Collectively, our findings identify p53 as a potential PTP4A2 substrate in leukemia cells and uncover a novel mechanism by which PTP4A2 enhances LIC maintenance.

After eight years and treatment with lenalidomide with excellent clinical response, she developed progressive cytopenias and transformation to acute myeloid leukemia, myelodysplasia-related (AML-MR)...The patient was treated with combination azacitidine and venetoclax and an investigational immunotherapy within a clinical trial...Our findings expand the spectrum of dmin-associated oncogenic amplifications in myeloid neoplasms and highlight FLI1 and ETS1 as recurrent targets of 11q24-derived ecDNA amplification. Recognition of such rare events underscores the importance of integrative cytogenomic profiling for uncovering novel mechanisms of leukemic transformation and potential therapeutic targets.

One such driver, ERG, displayed increased interactivity and expression in ETV6::RUNX1 B-ALL, and evidence suggests it plays a role in regulating survival and differentiation. Overall, these results underscore the essential role of 3D nuclear organization in acute leukemia.

P1/2, N=420, Recruiting, Janssen Research & Development, LLC | Trial completion date: May 2028 --> Sep 2030 | Trial primary completion date: Feb 2026 --> Jun 2026

We systematically synthesize recent clinical advances, from small-molecule inhibitors against protein-protein interactions (e.g., menin-KMT2A), to targeted degraders (PROTACs), epigenetic readers/writers inhibitors (e.g., BET, LSD1, DOT1L), and rational combination regimens with chemotherapy or immunotherapy. By integrating the biological characteristics of KMT2 with translational medicine and clinical evidence, this study provides a framework for advancing precision medicine approaches based on the molecular subtypes driven by KMT2.

At 8 years of age, both children remain in sustained molecular remission and enjoy age-appropriate development. This concordant twin pair illustrates the natural history of MLL-AF4-positive infant ALL, supports the curative potential of CAR-T-cell therapy in this ultra-high-risk population, and emphasises the importance of prolonged molecular surveillance.