azacitidine

P1, N=20, Not yet recruiting, Roswell Park Cancer Institute

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.

P1, N=30, Recruiting, OHSU Knight Cancer Institute | Trial completion date: May 2026 --> May 2028 | Trial primary completion date: Mar 2026 --> Mar 2027

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.

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.

P2, N=90, Not yet recruiting, Faron Pharmaceuticals Ltd

An 8-year-old female patient achieved bone marrow remission with azacitidine and venetoclax and subsequently underwent allogeneic hematopoietic stem cell transplantation from an unrelated umbilical cord blood donor, The conditioning regimen included fludarabine, decitabine, busulfan, and cyclophosphamide, leading to sustained donor engraftment. At the 13-month follow-up, the patient remained in complete hematologic remission without recurrence. This case suggests that allo-HSCT is a feasible curative option for children with high-risk MDS and germline DDX41 predisposition, highlighting the critical importance of screening potential donors for the same mutation.

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.

P2, N=226, Recruiting, The First Affiliated Hospital of Soochow University

P=N/A, N=50, Recruiting, The First Affiliated Hospital of Soochow University