NPM1 (Nucleophosmin 1)

The patient was treated with a modified MARIETTA protocol (without rituximab) and consolidated with a carmustine-based autologous stem cell transplant. shows complete metabolic response on PET-CT and MRI brain. This case presents the first successful treatment of a synchronous presentation of CNS and systemic ALK-positive ALCL, and the importance of a multidisciplinary approach for diagnosis.

NPM1 acts as an oncogenic driver in colorectal cancer by activating the AKT/mTOR signaling pathway. Elevated NPM1 expression highlights its potential as a diagnostic, prognostic, and therapeutic biomarker in CRC.

The patient achieved sustained remission following risk-adapted AML chemotherapy and allogeneic hematopoietic stem cell transplantation (allo-HSCT). This case underscores three critical points in pediatric AML: (1) the essential role of integrated molecular profiling in resolving morphologic ambiguities to prevent misclassification; (2) the complex prognostic impact of FLT3-ITD/NPM1 co-mutations in childhood AML; and (3) the potential therapeutic efficacy of allo-HSCT for rare fusion-driven subtypes.

AML with HOXB3 hypomethylation usually has unique genetic patterns such as a normal karyotype, cytogenetic/molecular-intermediate risk, and mutations in FLT3-ITD, NPM1 and DNMT3A. Despite these associations, HOXB3 hypomethylation may serve as an independent prognostic biomarker for AML.

Among these hub proteins, five proteins (NPM1, TOP2A, EZH2, PRKDC, and HNRNPK) were identified as clinically relevant when cross-referenced with the Human Protein Atlas database and the literature, highlighting their potential as diagnostic and therapeutic targets. These findings highlight the potential of nanoMIP-based snapshot imprinting as an alternative to 'classical' approaches for identifying potential protein targets for diagnostic and therapeutic applications.

In conclusion, our findings establish GAL3 and PDEδ, two KRAS-associated proteins, as promising combinatorial drug targets. Targeting these modulators provides an effective alternative strategy to overcome resistance mechanisms and enhance the clinical utility of existing KRAS inhibitors.

We evaluate the latest data on various menin inhibitors-both as monotherapy and in combinations-emphasizing their efficacy and safety profiles. As new evidence continues to accumulate with recent drug approvals and ongoing randomized, phase 3 studies, menin inhibitors are rapidly becoming a component of the AML treatment paradigm for relapsed/refractory and likely newly diagnosed disease.

The 4-year survival of AML with defective MDM2 inhibitor induced TP53-mediated apoptosis despite WT TP53 was dismal at 19% when NPM1 was co-mutated and 6% when NPM1 was WT. In summary, we identified prevalent multi-causal defects in TP53-mediated apoptosis in AML resulting in extremely poor patient survival.

In further studies, RNA sequencing confirmed the presence of NPM1::ALK gene fusion in this case; whole-exome sequencing (WES) detected somatic mutations in multiple genes of the JAK-STAT pathway (including JAK1, PTPN6, MTOR, and TYK2). It is noteworthy that such genetic alterations are more commonly observed in ALK-negative anaplastic large cell lymphoma (ALK-ALCL) but are less commonly reported in ALK+ALCL.

Our analysis of specific lncRNAs, such as HOTAIRM1, HOXB-AS3, CRNDE, HOXBLINC, LONA, IFEX9, XLOC_109948, and HOTTIP, enhances our understanding of the molecular mechanisms underlying AML in the context of NPM1c⁺. These findings lay the groundwork for developing targeted therapies and improved prognostic tools for NPM1c⁺AML.

Our study demonstrates that patients with eAML subtype have a worse prognosis, unique molecular features and higher tumor burden. Allo-HSCT might be an effective way to improve prognosis. This study provides evidence critical for risk stratification and treatment optimization in eAML.

Here we show that combination of niraparib and lenvatinib exhibits significant synergistic inhibitory effects against platinum-resistant OCCC cell lines, xenografts, patient-derived tumoroid (PDT) models, and prolonged survival in the platinum-refractory patient-derived xenograft (PDX) model. RNA sequencing revealed that the most differentially expressed genes in PDX models treated with this combination were associated with structural ribosomal components. This combination suppresses Src phosphorylation, NPM1 expression, and ribosomal protein levels in OCCC.