Our findings redefine epigenetic regulation in LUAD, demonstrating that regional methylation patterns-not global promoter status-orchestrate oncogene activation. We propose a novel framework for spatially resolved methylomics, advocating 1) dual-target assays monitoring both promoter and gene body methylation to improve diagnostic precision, and 2) therapeutic exploitation of SHOX2's intronic methylome as a druggable epigenetic switch.

NLR half reduction significantly predicted hematologic response (week 24 OR 6.42, p = 0.001) and molecular response consistently across all time points (week 24 OR 27.94, p < 0.001). NLR half reduction is a simple, cost-effective biomarker that may reflect molecular response and treatment efficacy in PV.

Clinical trials have demonstrated that ropeg-IFN reduces the JAK2 V617F allele burden, which is recognized as an independent risk factor for disease progression and thrombosis, apart from traditional factors such as age and prior cardiovascular events. To improve the prognosis of PV, it is essential to accumulate clinical evidence on trends in JAK2 V617F allele burden and the conditions required to maintain hematologic control after discontinuation of ropeg-IFN therapy in real-world settings.

The standard treatment is low-dose aspirin and phlebotomy, with cytoreductive therapy added for high-risk PV. All 3 patients achieved and maintained complete hematologic response with reduced JAK2 V617F allele burden. Ropeg-IFN is an effective and safe therapy for elderly patients with PV that also improves quality of life.

The patient maintained CHR and MR for 2 years following treatment discontinuation. We also discuss the potential benefit of ropeg-IFN in low-risk PV patients who were not previously considered candidates for aggressive cytoreductive therapy.

Ongoing treatment with hydroxyurea was substituted with ropeg (week 0: 250 mcg; week 2: 350 mcg; week 4 onwards: 500 mcg every 2 weeks). In conclusion, ropeg was safe and induced CHCR associated with significant molecular responses in patients with early MF. ClinicalTrials.gov Identifier: NCT04988815.

P2, N=35, Not yet recruiting, Jonsson Comprehensive Cancer Center

P3, N=1301, Active, not recruiting, National Cancer Institute (NCI) | Trial completion date: Jan 2026 --> Jan 2027

P3, N=1150, Active, not recruiting, ECOG-ACRIN Cancer Research Group | Trial completion date: Dec 2025 --> Dec 2026

P4, N=222, Not yet recruiting, Women’s Hospital, Zhejiang University School of Medicine; Women’s Hospital, Zhejiang University School of Medicine

This is the first study to provide pharmacokinetic evidence of RopegIFN exposure during pregnancy and lactation. These findings support the safety of RopegIFN use in pregnant ET and PV patients and highlight the need for a collaborative registry to collect real-world data and guide management for this high-risk population.

Combination therapy was reasonably well-tolerated but conferred marginal benefit in patients with metastatic melanoma. These results can inform future studies that employ recombinant IL-12 or novel IL-12 constructs.