NPM1 (Nucleophosmin 1)

P1/2, N=160, Recruiting, Sellas Life Sciences Group | Trial completion date: Dec 2025 --> Dec 2027 | Trial primary completion date: Dec 2025 --> Dec 2026

P3, N=1300, Recruiting, Kura Oncology, Inc. | N=719 --> 1300

We propose a prognostic risk model for HCC constructed using three prognostic model genes and provide computational evidence linking PF to key molecular nodes such as LDHA. External cohort validation and experimental studies are warranted.

DNMT3B functions as a context-dependent epigenetic regulator linking enhancer-associated chromatin organization with proliferative control and apoptotic resistance in AML. DNMT3B-directed epigenetic perturbation remodels cis-regulatory circuitry and is associated with increased venetoclax responsiveness, supporting DNMT3B-governed networks as a candidate co-targeting axis in high-risk AML.

P1, N=30, Recruiting, Uma Borate | Trial completion date: Dec 2025 --> Feb 2027 | Trial primary completion date: Dec 2025 --> Jan 2027

P2, N=70, Not yet recruiting, Uma Borate | Initiation date: Jan 2026 --> Apr 2026

Although treatment variables were not included and analysis focused on selected genes, these findings support incorporation of expression-based features into genetic risk models and warrant prospective validation. The authors have confirmed clinical trial registration is not needed for this submission.

Morphologic remission with undetectable measurable residual disease (MRD) by flow cytometry following revumenib was associated with improved overall survival, with a median of 23.6 months compared with 20.8 months in patients with morphologic response and detectable MRD, and 3.2 months in non-responders. In summary, treatment monitoring of AML by flow cytometry, following menin inhibition, requires recognition of phenotypic changes associated with differentiation.

This manuscript reviews the molecular rationale of menin inhibition for aberrant homeobox/myeloid ectopic insertion site 1 (HOX/MEIS1)-driven gene expression and leukemogenesis, clinical trial outcomes, and safety data for menin inhibitors, with a focus on recently FDA-approved revumenib and several other agents in development, ziftomenib (KO-539), bleximenib (JNJ-75276617), and icovamenib (BMF-219). We also focused our discussion on future directions to include resistance mechanisms, biomarker identification and monitoring strategies, and combination therapies. Menin inhibition is now being clinically integrated into relapsed/refractory and frontline treatment settings.

These findings provide preliminary evidence that integrating CNA/CN-LOH burden with mutational profiles may improve risk stratification in elderly patients with NPM1-mutated AML. However, given the small sample size, single-center design and lack of external validation, larger multi-center studies are warranted to assess the robustness of these findings.

In conclusion, this multicenter study suggests that most MS are of myelomonocytic/monoblastic origin, a high proportion of them are NPM1 mutated, and may lack expression of MPO and CD34. NPM1 mutation-specific antibodies should be integrated into the diagnostic panels for MS or LC, while IRF8 and PU.1 are not recommended as they cannot distinguish MS from histiocytic neoplasms.