In AML with 3q26.2 rearrangements (r) the distal GATA2 hematopoietic enhancer becomes aberrantly relocated leading to activation of EVI1 expression. In patient-derived xenograft (PDX) models of AML with MECOM-r, compared to each drug alone, co-treatment with FHD-286 and BETi OTX015 significantly reduced AML burden and improved survival, without inducing significant toxicity. These findings highlight the FHD-286-based combinations as promising therapy of AML with chromosome 3q26.2 rearrangement and EVI1 overexpression.

Initial treatment began with azacitidine, a hypomethylating agent...However, there is no consensus on its management, and the role of systemic chemotherapy remains debated. Continuous monitoring for progression to acute myeloid leukemia (AML) is crucial, as early detection significantly impacts prognosis and informs treatment decisions.

P=N/A, N=20, Active, not recruiting, Hikma Pharmaceuticals LLC | Not yet recruiting --> Active, not recruiting

Chemoresistance in BC involves extensive genomic and epigenetic remodeling. Although DAC can modulate methylation and tumor phenotype, rational drug combinations will be required to overcome resistance.

P1, N=35, Active, not recruiting, Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins | Recruiting --> Active, not recruiting | Trial completion date: Dec 2026 --> Jul 2027 | Trial primary completion date: Jan 2026 --> Sep 2026

P1/2, N=42, Recruiting, M.D. Anderson Cancer Center | Trial completion date: Jan 2026 --> Jan 2028 | Trial primary completion date: Jan 2026 --> Jan 2028

P1, N=2, Terminated, Bristol-Myers Squibb | N=32 --> 2 | Active, not recruiting --> Terminated; Insufficient Enrollment

The 15-day venetoclax plus azacitidine regimen demonstrated high efficacy and manageable toxicity in treatment-naïve HR-MDS. It may be particularly beneficial for patients with high neutrophil counts, adverse cytogenetics, or those eligible for HSCT, supporting further investigation in larger trials.

Importantly, peripheral blood BTG1 mRNA expression levels reliably predicted therapeutic response to decitabine, establishing BTG1 as a robust biomarker of decitabine efficacy in AML management. Clinical trial registration: ChiCTR2000037928.

However, the need for longer follow-up and expanded cohorts remains critical to validate these outcomes and optimize patient selection. These findings support the further exploration of venetoclax and azacitidine as a viable treatment option for patients with refractory or high-risk multiple myeloma, warranting additional prospective trials before consideration for standard-of-care implementation.

TP53 mutations drive DAC resistance via epigenetic reprogramming. Targeting these genes may improve outcomes in TP53 -mutated MDS.

These findings indicate that DNMT1 and DNMT3A drive hepatocellular carcinoma through epigenetic regulation and are viable prognostic biomarkers. Targeting these enzymes with 5-azacytidine offers a promising therapeutic strategy for hepatocellular carcinoma management.