NPM1 (Nucleophosmin 1)

These co-regulated proteins highlight the integration of BRAF signaling with critical processes, such as cell cycle control, apoptosis, DNA damage response, and protein synthesis in melanoma. Our analysis suggests that targeting BRAF-interacting proteins may also modulate oncogenic signaling pathways and represent promising biomarkers for melanoma diagnosis and therapy.

The menin-lysine methyltransferase 2A acute leukemia (KMT2A) protein-protein interaction has emerged as a clinically validated epigenetic target in acute leukemia, following the approval of the reversible menin inhibitor Revumenib for KMT2A-rearranged and nucleophosmin 1 (NPM1)-mutant disease...Across all chemical classes, sustained target engagement-rather than equilibrium affinity alone-emerges as the dominant determinant of antileukemic efficacy. By integrating structure-activity relationship (SAR), resistance mechanisms, safety considerations, and translational scope across oncology and metabolic indications, this review provides a roadmap for the rational design of next-generation menin inhibitors and establishes menin as a model system for modern epigenetic drug discovery.

Not available.

We critically evaluate the preclinical and clinical development of menin inhibitors, including revumenib, ziftomenib, bleximinib, and icovamenib, summarizing efficacy signals in relapsed/refractory disease, safety profiles, and emerging resistance mechanisms. Special attention is given to combination strategies with venetoclax, FLT3 inhibitors, chemotherapy, and epigenetic agents, which aim to enhance response durability and mitigate resistance. Finally, we discuss ongoing clinical trials, unresolved challenges in patient selection and sequencing, and future directions for integrating menin inhibition into precision-based treatment paradigms for acute leukemia.

P2, N=29, Active, not recruiting, Grupo Cooperativo de Estudio y Tratamiento de las Leucemias Agudas y Mielodisplasias | Recruiting --> Active, not recruiting

P2, N=35, Not yet recruiting, Second Affiliated Hospital, School of Medicine, Zhejiang University

Measurable residual disease (MRD) assessment using multiparameter flow cytometry and molecular assays is increasingly used to refine post-remission decisions, including transplantation and maintenance strategies, but is constrained by assay variability, clonal hematopoiesis, and limited evidence for MRD-directed interventions. This narrative review synthesizes the evolving genomic landscape, guideline-endorsed targeted therapies, and investigational strategies in AML, and provides a practical framework that integrates genomic profiling, MRD-informed decision-making, and algorithmic treatment pathways while highlighting real-world barriers to implementation and equity.

P=N/A, N=100, Recruiting, Peking University People's Hospital

The LCM-PICR workflow provides a rapid and sensitive sample processing strategy for LC-MS/MS-based spatial proteomics from micrometer-scale tissue regions. This approach supports detection of spatially structured protein variation within tumors and offers a practical tool for studying intratumoral heterogeneity and spatially resolved disease biology.

Additionally, nucleophosmin 1 (NPM1) significantly enhances the transcriptional activation of TNFAIP6 and associates with the -2000 to -1700 bp region of its promoter. These findings delineate a regulatory model in which lung adenocarcinoma cells directly stimulate NETosis through the NPM1-TNFAIP6-CD44-SPP1 axis, suggesting that therapeutic targeting of this pathway may attenuate tumor progression.

While subtypes of AML are increasingly defined by druggable driver mutations including FLT3-ITD, IDH1, IDH2, and NPM1, conventional chemotherapy and reduced intensity induction regimens (e.g., azacitidine-venetoclax) remain therapeutic backbones. Current understanding of AML biology and state-of-the-art tools for MRD measurement are reviewed here in an effort to promote clinical and laboratory investigator collaboration for the development of reliable tools for improving outcomes in this deadly disease. Clinical trial number: not applicable.