This classifier outperformed a previously developed gene signature in a second MDS patient cohort, but signatures of hematological responses were unable to predict survival. Overall, these studies characterize the molecular consequences of AZA treatment in MDS HSPCs and identify a potential tool for predicting AZA therapy responses and overall survival prior to initiation of therapy.

Differentiation of ADSCs was induced by using 3 μg/mL 5-azacytidine for 24 hours...Coculturing PC12 cells and ADSCs improves the efficiency of myogenic differentiation. However, the effectiveness of myogenic differentiation depends on the proportions of administered PC12 cells.

The SLC22A17 methDNA hotspot could represent a promising biomarker for CM, highlighting the regulatory role of methDNA on SLC22A17 expression. These results pave the way for the identification of novel epigenetic biomarkers and therapeutic targets for the management of CM patients.

This includes azacitidine, currently approved for myelodysplastic neoplasms (MDS), novel UBA1 inhibitors being developed for a broad spectrum of cancers, Protein Kinase R-like Endoplasmic Reticulum Kinase (PERK) inhibitors, and auranofin, a long-established drug for rheumatoid arthritis. This perspective bridges basic research to clinical symptoms and therapeutics.

When patients with a recurrence of AML have a history of consuming or contacting aquatic products, clinicians should be vigilant about Aeromonas veronii infection. The presence of Aeromonas veronii in peripheral blood must alert clinicians to the possibility of severe sepsis and septic shock. Early diagnosis and prompt treatment are crucial to reducing patient mortality.

P=N/A, N=60, Recruiting, Nantes University Hospital | Not yet recruiting --> Recruiting | Initiation date: Jun 2024 --> Sep 2024 | Trial primary completion date: Apr 2026 --> Jul 2026

P2, N=40, Not yet recruiting, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine

P=N/A, N=43, Recruiting, The First Affiliated Hospital of Soochow University | Trial primary completion date: Jul 2024 --> Jul 2025

The incidence of bone marrow suppression and pneumonia in the decitabine group was higher compared with that in the azacitidine group. Continuous and regular use of appropriate doses of hypomethylating agents may benefit MDS patients to the greatest extent if it is tolerated.

AML with RARG rearrangement is insensitive to all-trans retinoic acid (ATRA) and arsenic trioxide. The patient received azacitidine therapy after failing ATRA and standard 3 + 7 therapy (idarubicin and cytarabine) and achieved complete remission. Conclusively, this acute myeloid leukemia subtype may benefit from azacitidine.

P1, N=20, Not yet recruiting, Baylor College of Medicine

DRI and WT1 expression associate significantly with OS after AZA/DLI. Hence, WT1 may represent an MRD marker, especially in CR patients at high risk.

P=N/A, N=20, Not yet recruiting, Hikma Pharmaceuticals LLC

Treatment for PTCL traditionally starts with the CHOP regimen (cyclophosphamide, doxorubicin, vincristine, and prednisone). We present a case of a patient with PTCL-NOS who progressed despite multiple treatment regimens, including both traditional and novel therapeutic agents, and finally achieved good results with azacytidine, selected based on a TET2 mutation. This case proposes future research into Azacytidine's efficacy in this patient population and further exploration of the broader utility of epigenetic therapies in PTCL.

Our study shows the restoration of CD34 FDC post-DLI is associated with reduced relapse and improved overall survival, with low NRM.

Repression of immune genes was reversed by inhibiting DNA methylation using low-dose decitabine, which suppressed tumor growth and restored immune control, increasing the number, functionality and memory of tumor-infiltrating lymphocytes and reducing the number of myeloid suppressor cells. Decitabine induced important interferon, pyroptosis and necroptosis genes, inflammatory cell death and immune control in GEMM and implanted breast and melanoma tumors.

All patients (5/5) treated with 5-azacitidine alone and one of the four treated with 6-mercaptopurine monotherapy had a reduction in mutant variant allele frequency. Among patients who received transplants, 7/13 are alive, and relapse post-transplant occurred in 3/13 with a median time to relapse of 3.55 months. This report provides insight into therapy responses and long-term outcomes across different genetic subsets of JMML and lends insight into the expected time to spontaneous resolution in patients with NS-MPD with germline PTPN11 mutations.

The development of medicine, especially in oncology, has led to an increased possibility of developing multiple cancers. Clinically, some doctors may not be aware of the existence of multiple primary cancers, especially simultaneous carcinomas, which can be easily missed or misdiagnosed.

No abstract available

This study uncovered the mechanism of promoter methylation mediated TERT activation in TERT promoter mutation-negative thyroid cancer cells and indicated TERT upstream promoter methylation as a therapeutic target for thyroid cancer.

P2, N=268, Completed, M.D. Anderson Cancer Center | Active, not recruiting --> Completed | Trial completion date: Oct 2027 --> Jul 2024 | Trial primary completion date: Oct 2026 --> Jul 2024

Our results indicate that while 5-aza is a useful drug for treating haematological cancers, surviving cancer cells that have been exposed to lower doses of the drug may activate mechanisms such as ALT. This could lead to cancer cell survival and possible resistance to 5-aza clinically.

DNMT1 gene deletion made cancer cells prone to TET2 upregulation and activation of tumor suppressor expression upon DNMT inhibitor challenge. TET2 augmentation is concomitant with resistance to DNMT inhibitors in a DNMT1-deleted state.

We found that the epigenetic inhibitor 5-Azacytidine (5-Aza) upregulated gasdermin E (GSDME) expression at the gene level, whereas the oHSV decreased the ubiquitination and degradation of GSDME to elevate its levels...Additionally, the combination therapy of ACNPs and oHSV effectively inhibited tumor growth, remodeled the immunosuppressive TME, and improved the efficacy of immune checkpoint blockade (ICB) therapy. These results demonstrate the potential to overcome immunosuppression through synergistic combinations, offering a promising approach for cancer immunotherapy.

The same clonal mutations in SRSF2, IDH1, and RUNX1 were found in both skin and BM with resolution of the lesions after the initiation of azacytidine. In conclusion, we report an exceptional case in which specific granulomatous cutaneous lesions have preceded and allowed the earlier diagnosis of an underlying CMML and a review of all previous similar cases in the literature, including molecular alterations.

The combination of azacitidine with IFN-α was well-tolerated with no observed severe myelotoxicity, and the majority of adverse events were reversible and manageable. In conclusion, the use of azacitidine in conjunction with IFN-α as pre-emptive therapy is a safe and effective treatment to prevent disease progression in AML/MDS patients with MRD positivity post-allo-HSCT.

Methionine restriction with rMETase up-regulates PD-L1 expression in human colorectal cancer cells and the combination of rMETase and ICIs may have the potential to improve immunotherapy in human colorectal cancer.

Here, we evaluated whether some miRNs may affect tumor development comparing untreated and 5-azacitidine (5-AZA) MDS-treated patients...Although our study was limited by the low number of MDS patients included, we identified miRN deregulation involved in MDS development that could regulate redox sensors and inflammatory responses. Finally, 5-AZA treatment is related with lower miRN expression levels in MDS patients.

P=N/A, N=30, Not yet recruiting, Peking University People's Hospital | Trial completion date: Dec 2026 --> Dec 2027 | Trial primary completion date: Dec 2025 --> Dec 2026

P1/2, N=52, Recruiting, Navy General Hospital, Beijing | Initiation date: Mar 2024 --> Aug 2024

Early HbF induction is featured as an accessible prognostic indicator for HMA treatment and the proposed potential epigenetic mechanism of HbF re-expression in azacytidine responders includes hypomethylation of the γ-globin gene promoter region and hypermethylation of the CpG326 island of ZBTB7A. The association of these methylation patterns with blast clearance and their prognostic value for PFS paves the way to discuss in-depth azacytidine epigenetic mechanism of action.

Briefly, our study discovered DUSP5 which was regulated by epigenetic modification, might be a potential therapeutic target, especially in LUAD patients with acquired EGFR-TKI resistance.

Azacitidine is safe and results in decreased DNA methylation of PBMCs in infants with KMT2A-r ALL, but the incorporation of azacitidine to enhance cytotoxicity did not impact survival. Clinicaltrials.gov identifier: NCT02828358.

Deletion of Dck, the rate-limiting enzyme for the cytidine salvage pathway, eliminated C>G transversions. Taken together, these findings demonstrate a highly penetrant mutagenic and leukemogenic phenotype associated with ATC.

P=N/A, N=60, Not yet recruiting, Nantes University Hospital

P1, N=27, Suspended, National Cancer Institute (NCI) | Trial completion date: Aug 2024 --> May 2028 | Trial primary completion date: Aug 2024 --> May 2027

P1, N=48, Recruiting, Novo Nordisk A/S | Not yet recruiting --> Recruiting

We showed that DNA methylation causes the silencing of TIMP2 and TIMP3 in invasive PA, it can also lead to malignant cell proliferation and cause pathological changes, whereas the use of 5-AzaC can inhibit the methylation process and can inhibit cell proliferation. Our results provide a novel method for clinical diagnosis and prevention of invasive PA.

Less intensive chemotherapy using azacitidine or cytarabine was selected for all patients with WT1 increase and 12 (60%) with hematological relapse. The 1-year overall survival and event-free survival rates for WT1 increase and hematological relapse were 70% vs. 44% (P = 0.024) and 70% vs. 29% (P = 0.029), respectively. These real-world data suggest that WT1-guided pre-emptive therapy may be superior to therapy after hematological relapse in patients with AML who have undergone allo-HSCT.

No abstract available

P2; Trial completion date: May 2024 --> May 2026 | Trial primary completion date: May 2024 --> May 2026

Unfortunately, irreversible nucleoside inhibitors (azacytidine and decitabine) have proven highly cytotoxic, and competitive inhibitors are also problematic. This work describes synthetic and structural investigations of a new class of allosteric DNA methyltransferase 3A (DNMT3A) inhibitors, leading to the identification of several critical pharmacophores in the lead structure. Specifically, we find that the tetrazole and phthalazinone moieties are indispensable for the inhibitory activity of DNMT3A and elucidate other modifiable regions in the lead compound.