Therapeutically, combinatorial targeting of MTHFD2 with its selective inhibitor and the hypomethylating agent decitabine induced ferroptosis in patient-derived IDH-mut glioma organoids, demonstrating potent ferroptosis activation. This work delineates an RNA epitranscriptomic-metabolism axis in glioma pathogenesis and provides a translational roadmap for exploiting metabolic dependencies in IDH-driven malignancies. CLINICAL TRIAL NUMBER: Not applicable.

Moreover, DEK deletion enhances LSC chemosensitivity to the standard-of-care combination of azacitidine and venetoclax (Aza/Ven), whereas DEK overexpression confers robust chemoresistance. Furthermore, combining CX-4945 with venetoclax promotes LSC apoptosis and represses the PBX3-driven leukemogenic transcriptional program, exhibiting synergistic anti-AML effects both in vitro and in vivo. Collectively, our findings uncover a previously unrecognized phosphorylation event (DEK-4S phosphorylation) that sustains LSCs and establish the CK2-DEK axis as a promising LSC-specific therapeutic strategy for AML.

Mechanistically, Aza induces epigenetic reprogramming in T cells and increases the expression of a stem-like precursor marker, TCF7. By shifting the focus on T cell biology, our study provides a rationale for combining Aza with other immunotherapies that can enhance durable immune responses in this malignancy.

Treatment of human sarcoma lines with decitabine and entinostat induced similar gene expression changes, including shared antigen targets, and increased MHC I expression. These findings demonstrate that epigenetically upregulated antigens can serve as effective tumor-specific targets and broaden immunotherapy strategies for low-mutation sarcomas.

Here, we propose and implement a temporal immunomodulation via methylation epigenetics (TIME) strategy through the combined intravenous administration of the FDA-approved small-molecule drug azacitidine and a BP/siPRMT1 nanocomplex...This "Ignite-Sustain" feature enables rapid immune sensitization and long-term immune maintenance. Compared to the delivery of an epi-drug or nucleic acid drug alone, the TIME strategy effectively expands the critical time window for immune activation, achieving durable and controllable tumor immunotherapy.

Recently, the randomized phase III VERONA study evaluating azacitidine plus venetoclax (VEN) versus azacitidine plus placebo in newly diagnosed HR-MDS showed no difference in overall survival (OS) between the two arms. However, we did not observe a statistically significant difference in OS for HMA/VEN vs. HMA monotherapy (Hazard Ratio [HR]: 0.83; 95% CI: 0.64-1.07; p = 0.15). In subgroup analyses, patients with TP53 wild-type disease (HR: 0.47; 95% CI: 0.29-0.74; p = 0.002) had a significant improvement in OS and those with ≥10% bone marrow blasts (HR: 0.73; 95% CI: 0.53-1.01; p = 0.06) had a trend towards OS benefit with HMA/VEN.

Leukemia therapy, especially myelogenous leukemias, is often challenged by an aggressive nature, high relapse rate due to dormant stem cells, side effects, and drug resistance. Additionally, H62, like the DNMT inhibitor 5-Azacytidine, suppressed β-tubulin in leukemic cells. These results suggest that the H62 compound possesses unique dual DNMT and microtubules-inhibitory activity through binding to DNMT and β-tubulin, making it a potent candidate for the treatment of myelogenous leukemias, including erythroleukemia with an unfavorable prognosis.

TET promoter‑wide 5‑mC and 5‑hmC profiles were compared in CD138+ sorted cells from newly diagnosed and relapsed patients with MM and in five myeloma cell lines treated with 5‑azacytidine and/or 5‑aza‑2'‑deoxycytidine...Notably, the divergent expression patterns observed suggest that TET1 acts as an oncogenic driver, while the inducible response of TET2 highlights its role as a potential tumor suppressor in myeloma biology. Consequently, the present results provide a rationale for the pharmacological restoration of TET2 expression as a strategic approach to suppress tumor progression through epigenetic reprogramming.

Oral azacitidine (CC-486) demonstrated overall survival benefit in older patients in first complete remission who were not transplant candidates, establishing a standard of care in this population. In FLT3-mutated AML, post-transplant maintenance with sorafenib and gilteritinib reduces relapse risk, with emerging evidence supporting MRD as a predictive biomarker for benefit. Other targeted agents and immunotherapies have shown promising early-phase results, although confirmatory data are limited. Ongoing phase III studies will clarify optimal patient selection, treatment duration, and integration with transplantation, aiming to transform post-remission management from passive surveillance to precision-based relapse prevention.

P=N/A, N=100, Completed, Centre Hospitalier Universitaire de Nice | Recruiting --> Completed | Trial completion date: Jan 2025 --> Jun 2026 | Trial primary completion date: Jan 2025 --> Oct 2025

P2, N=40, Recruiting, University of Illinois at Chicago | Trial completion date: May 2026 --> May 2027 | Trial primary completion date: May 2026 --> May 2027

Across all measured trajectory metrics, backbone RMSD, residue fluctuation, radius of gyration, solvent-accessible surface area, and intermolecular hydrogen bond count, Wogonin formed a more stable, compact complex. These findings suggest that Wogonin and Xanthohumol are non-toxic nutraceutical candidates suitable for DNMT1 targeted epigenetic therapy, with computational foundation strong enough to facilitate future in vitro and in vivo validation work.