IDH2 (Isocitrate Dehydrogenase (NADP(+)) 2)

Robust nuclear expressions of ACO2 and IDH2 drive aggressive tumors indicating the tumorigenic potential of IDH2-ACO2-KAT2A axis. Altogether, our work reveals a paradigm coupling a nuclear metabolic pathway with histone acetylation to control of gene expression that accentuates hyperproliferative phenotype in tumors.

We discuss the biological rationale for combination approaches and summarize the key clinical studies that have defined current practice, including trials evaluating FLT3 inhibitors, gemtuzumab ozogamicin, IDH inhibitors, and venetoclax-based strategies. While genotype-directed strategies-such as FLT3 inhibition-have already demonstrated survival benefit, optimal patient selection, treatment sequencing, and duration remain areas of active investigation. Future progress will likely depend on MRD-driven treatment adaptation, improved understanding of clonal evolution, and the development of rational multi-agent combinations capable of achieving deeper and more durable remissions.

This review synthesizes current evidence on the roles of IDH1/2 mutations and dysregulation of AXL signaling in CS, emphasizing their potential contributions to tumor aggressiveness, immune suppression, and resistance to therapy. Additionally, we explore current developments in targeted therapy exploiting IDH1/2 and AXL dysregulation.

P2, N=148, Not yet recruiting, Shen yang

This case raises the possibility of an association between Maffucci syndrome and recurrent papillary breast lesions. In the absence of molecular confirmation, this relationship remains speculative and should be regarded as hypothesis generating, underscoring the need for further investigation with genetic and immunohistochemical correlation rather than changes to established breast cancer screening guidelines.

P1/2, N=33, Recruiting, Mayo Clinic | Not yet recruiting --> Recruiting

This selected real-world cohort demonstrates durable responses exceeding published benchmarks and has one of the longest follow-up periods reported for IDHi in AML. A subset of older adults with IDH-mutated AML can achieve highly durable remissions on IDHi without significant toxicity.

P1, N=15, Recruiting, Memorial Sloan Kettering Cancer Center | Trial completion date: Aug 2026 --> Dec 2026 | Trial primary completion date: Aug 2026 --> Dec 2026

We observed substantial rewiring of epigenetic cofactor-related MG expression in CCAs. Functional assays validated new targets among EpiGs (e.g., CBX3, CHD4, DEK, SMARCA4, and TRIM28) and MGs (TYMS and IDH2) in CCA.

Lastly, epigenetic analyses of histone marks revealed that IDH1 induces widespread alterations in histone acetylation and tri-methylation. Our results highlight a novel role for IDH1 in cardiac metabolism and transcriptional control of metabolic adaptation to tumor-mediated stress and provide evidence that reductive-citrate formation may induce epigenetic modifications in the heart.

This model provides a robust and interpretable tool for individualized risk stratification in elderly AML. By integrating genomic, immunophenotypic, and therapeutic variables, it may help optimize treatment decisions and improve outcomes for this vulnerable population. Future efforts should focus on external validation and integration of dynamic biomarkers.