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.

We show that the treatment with cAzadC goes in hand with the broad reactivation of the cellular antitumor responses. With patient-derived xenograft AML-mouse models, we show that this translates into a strongly improved anticancer effect in vivo.

Overexpression of anti-apoptotic protein BCL-2 and hypermethylation are hallmarks of acute lymphoblastic leukemia (ALL) and can be pharmacologically addressed by venetoclax (VEN) and hypomethylating agents (HMA) such as azacytidine (AZA) or decitabine (DEC). AZA-induced metabolic suppression as well as overall anti-leukemic activity alone and in combination with VEN was generally weaker compared to DEC. Altogether, we herein demonstrate that combined VEN and HMA application acts synergistically and significantly reduces the leukemic burden in ALL cell lines via impairment of tumor cell metabolism and mitochondrial function.

These findings suggest that chronic inflammatory and senescent microenvironmental states constrain effective immune activation despite combined epigenetic and immune checkpoint therapy. Here, we identify distinct bone marrow microenvironments associated with patient survival after combined epigenetic and immune checkpoint therapy and suggest candidate biomarkers to guide patient stratification in HMA-R/R MDS.

Azacitidine was administered after dialysis sessions, while venetoclax dosing was adjusted because of concomitant posaconazole prophylaxis. Approximately one year after diagnosis, relapsed AML was identified on peripheral blood flow cytometry. This case highlights the feasibility of venetoclax-based lower-intensity therapy in selected dialysis-dependent AML patients while underscoring the persistent therapeutic limitations and adverse prognosis associated with relapsed disease in this population.

P1, N=9, Not yet recruiting, Fred Hutchinson Cancer Center

While currently, hypomethylating agent therapy (azacitidine and decitabine) is mainly used in high-risk MDS patients, and ruxolitinib is primarily used in symptomatic primary myelofibrosis (PMF-MPN), their clinical efficacy remains suboptimal. In response, a new generation of immune checkpoint inhibitors are being developed to target the TME, including PD-1/CTLA-4 blockers, macrophage-directed agents including CD47 inhibitors, and T cell-targeting checkpoint inhibitors such as TIM-1 and LAG-3. This review will describe the functional role of key TME constituents in the progression of myeloid malignancies and explore the current landscape and future potential of advanced cellular and molecular immunotherapies in the treatment of these disorders.

c-Myc activation is a key driver of VEN resistance in t(8;21) AML. HHT acts as a mechanistically complementary agent, restoring VEN sensitivity. These results provide a preclinical rationale for clinical evaluation of VEN-HHT combination therapy in genetically defined AML subsets.

P3, N=93, Completed, Celgene | Active, not recruiting --> Completed

Despite CHOP, CHOEP, DA-EPOCH, and AC-CHOP (azacitidine plus chidamide) regimens, the patient experienced primary refractory disease and died 6 months from diagnosis following COVID-19 superinfection. To our knowledge, this is the first case reporting single-cell transcriptomic comparison of skin versus blood compartments in PTCL-NOS, revealing how cutaneous microenvironment sculpts aggressive malignant phenotypes and providing potential targets for compartment-specific therapy.

This combination was associated with high response rates and durable remissions, with an acceptable safety, in heavily pretreated patients with AML harboring alterations susceptible to menin inhibition.