PLCG2 (Phospholipase C Gamma 2)

Moreover, upon ibrutinib treatment, REL DNA-binding activity decreased in 2pWT CLL cells but remained sustained in 2p+ CLL cells following BCR stimulation, suggesting that persistent NF-κB activation contributes to resistance...Altogether, our study identifies REL overexpression as a novel 2p+-driven mechanism of BTKi resistance in CLL, complementing the well described BTK and PLCG2 mutations. These findings support the clinical relevance of detecting 2p gain to guide treatment strategies and improve outcomes in CLL.

This study revealed for the first time the heterogeneity of palmitoylation at the GBM single-cell level. The identification of ZDHHC2, ZDHHC4, and ZDHHC20 as key regulators of palmitoylation in GBM emphasized their potential as biomarkers and therapeutic targets.

Considering the rarity and heterogeneity of WT-GISTs, a regulatory detection procedure should be established for WT-GISTs, including NGS for qWT-GISTs, to identify the molecular mechanisms and potential therapeutic targets. Implications: WT-GISTs are heterogenous tumors which should be managed using different treatments and follow-up strategies.

The findings indicate that Liquiritigenin inhibits platelet activation by targeting P2Y12R. This action disrupts the Src/PLCγ2 signaling pathway and subsequently reduces cytoplasmic calcium mobilization. These results suggest that Liquiritigenin may have therapeutic potential for the treatment of thrombotic diseases associated with platelet activation.

In vivo, PLCG2 silencing suppressed SCLC tumor growth. In conclusion, PLCG2 is a promising biomarker for SCLC diagnosis and might be a potential therapeutic target, with its interaction with VCP playing a role in SCLC cell survival and mitophagy.

This study highlights the complex clonal dynamics of BTK mutations in R/R CLL patients undergoing pirtobrutinib treatment, and the extent of resistance without an obvious genomic driver. NCT03740529.

While sensitivity of these variants to physiological nucleotide inhibition is reduced, we identified artificial nucleotide compounds that can inhibit such variants not only in vitro but also in cell-based assays. Therefore, our findings suggest a route for development of isozyme specific PLCγ inhibitors allowing further studies of their roles in health and disease.

Findings confirm that NHL, particularly DLBCL, is the most prevalent malignancy in this cohort. Given the link between malignancies and underlying IEI, immunologic evaluation is recommended, particularly for NHL patients. The observed predominance of hematologic malignancies among CVID patients and the association with lymphoproliferation further emphasize the need for heightened malignancy surveillance and early immunologic workup in this subgroup. Further research on biomarkers for malignancy prediction in IEI is warranted.

Our findings establish KMCG as a novel biomarker integrating thrombotic risk and tumor progression, while mechanistically linking KRAS-G12D-driven MAPK activation to both cancer metastasis and thrombosis. This dual regulatory axis provides therapeutic targets for simultaneously managing thrombotic complications and malignant progression in KRAS-mutant CRC.

Furthermore, drug sensitivity analysis indicated that the high-risk group exhibited increased sensitivity to Axitinib, while the low-risk group showed higher responsiveness to drugs such as cisplatin. It not only serves as a predictor of patient survival but also provides a theoretical foundation for personalized immunotherapy and drug selection. Future research should focus on further validating the clinical applicability of this model and exploring its potential in the context of immunotherapy and targeted therapies.

This bioinformatics study delineates key matrisome-associated genes and pathways in HBV-related cirrhosis, offering novel insights into potential biomarkers and therapeutic targets. Further validation in larger cohorts is warranted to confirm clinical relevance.

Interestingly, the abnormal protein expression of FLOT2 in blood CD14+ cells distinguished early-stage malignant breast cancer patients from people with benign breast tumors. In summary, our findings reveal Flot2-siRNA as a potential inhibitor of pathological osteoclastogenesis to treat osteolytic diseases, and identify FLOT2 protein in peripheral osteoclast precursor cells as a novel marker to facilitate early diagnosis of breast cancer, especially in premenopausal women.