Interplay between proteasome inhibitors and NF-κB pathway in leukemia and lymphoma: a comprehensive review on challenges ahead of proteasome inhibitors.

The current scientific literature has extensively explored the potential role of proteasome inhibitors (PIs) in the NF-κB pathway of leukemia and lymphoma. The ubiquitin-proteasome system (UPS) is a critical component in regulating protein degradation in eukaryotic cells. PIs, such as BTZ, are used to target the 26S proteasome in hematologic malignancies, resulting in the prevention of the degradation of tumor suppressor proteins, the activation of intrinsic mitochondrial-dependent cell death, and the inhibition of the NF-κB signaling pathway. NF-κB is a transcription factor that plays a critical role in the regulation of apoptosis, cell proliferation, differentiation, inflammation, angiogenesis, and tumor migration. Despite the successful use of PIs in various hematologic malignancies, there are limitations such as resistant to these inhibitors. Some reports suggest that PIs can induce NF-κB activation, which increases the survival of malignant cells. This article discusses the various aspects of PIs' effects on the NF-κB pathway and their limitations. Video Abstract.

Genetic variants of dectin-1 and their antifungal immunity impact in hematologic malignancies: A comprehensive systematic review.

BACKGROUND: Fungal infections pose a significant threat to individuals with hematologic malignancies due to compromised immune systems. Dectin-1, a pivotal pattern recognition receptor, plays a central role in antifungal immune responses. Understanding its genetic variants' impact is crucial for advancing personalized therapeutic approaches. METHODS: Employing systematic review methods, studies were meticulously selected and assessed for relevance. Data extraction encompassed Dectin-1 genetic variants, antifungal immune responses, and disease outcomes. RESULTS: Findings unveiled a complex relationship between Dectin-1 genetic variants and antifungal immunity in hematologic malignancies. Variable associations emerged, influencing susceptibility to fungal infections and disease prognosis. Moreover, implications for treatment outcomes were explored, suggesting potential avenues for tailored interventions. CONCLUSIONS: This systematic review underscores the need for further investigation into the precise influence of Dectin-1 genetic variants on antifungal immunity and disease progression in hematologic malignancies. Insights gained could pave the way for personalized therapeutic strategies, optimizing infection prevention and malignancy management. By delving into the intricate connections between genetic nuances, immune responses, and clinical trajectories, this review contributes to the ongoing discourse surrounding hematologic malignancies, fungal infections, and their multifaceted interplay.