Azacitidine is an anticancer drug used to treat myelodysplastic syndromes (MDS), chronic myelomonocytic leukemia (CMML), and certain patients with acute myeloid leukemia (AML) who cannot undergo intensive chemotherapy. It is also approved for children with juvenile myelomonocytic leukemia (JMML) before stem cell transplantation to help control the disease.

Azacitidine works by reducing DNA methylation and directly damaging abnormal blood-forming cells. At low doses, it blocks DNA methyltransferase enzymes, helping reactivate tumor suppressor genes. At higher doses, it disrupts RNA and protein production, leading to cell death. These actions slow abnormal cell growth and trigger apoptosis in malignant cells.

Azacitidine is given either subcutaneously or intravenously, usually once daily for seven days in a 28-day cycle. The subcutaneous route is commonly used in outpatient care, while IV administration is chosen when needed. Doses vary based on body surface area, kidney function, and blood counts, and treatment must be supervised by an experienced healthcare professional.

Azacitidine can cause nausea, vomiting, diarrhea, constipation, fatigue, and injection site reactions. Blood-related side effects like anemia, neutropenia, and thrombocytopenia are common and may raise the risk of infections or bleeding. Less frequent effects include fever, rash, dizziness, and elevated liver enzymes, while serious reactions such as kidney or liver problems are rare. Regular monitoring of blood counts and organ function is important during treatment.

Azacitidine is contraindicated in patients allergic to it or to mannitol, and it should not be used in those with advanced malignant liver tumors. Caution is needed in people with liver or kidney problems, as well as those at risk of infection or bleeding due to its myelosuppressive effects. Regular blood count monitoring is essential. The drug is not recommended during pregnancy or breastfeeding, and effective contraception is required during and after treatment.

Azacitidine is a key treatment for MDS, AML, CMML, and JMML, working through both epigenetic effects and direct cytotoxicity to control abnormal cell growth. While generally well tolerated, it requires close monitoring due to blood-related and systemic side effects. When used under expert care, it can greatly improve outcomes and quality of life for suitable patients.

Azacitidine incorporates into both RNA and DNA, affecting RNA metabolism and inhibiting DNA methylation, whereas decitabine integrates only into DNA and primarily inhibits DNA methyltransferase. Clinically, both are used in similar hematologic conditions, but azacitidine is often favored for its broader epigenetic activity and has demonstrated improved overall survival in some studies.

In juvenile myelomonocytic leukemia (JMML), azacitidine is used prior to hematopoietic stem cell transplantation to reduce disease burden and improve transplant outcomes. Clinical trials such as AZA-JMML-001 have shown that it can induce hematologic and molecular responses that enhance transplant success rates.

Response is typically assessed using bone marrow examinations, complete blood counts, and cytogenetic or molecular studies. Since azacitidine may take several cycles to show efficacy, treatment is usually continued for at least 4–6 cycles before determining response or failure, unless there is clear disease progression or intolerance.

Yes, azacitidine is being investigated in combination with other agents such as venetoclax, especially in older AML patients unfit for intensive chemotherapy. These combinations have shown synergistic activity and improved response rates, but they also carry increased risk of myelosuppression and infections.

Resistance to azacitidine may occur due to upregulation of cytidine deaminase (which inactivates the drug), changes in nucleoside transporters, or clonal evolution of resistant cell populations. Strategies to overcome resistance include combination therapies, sequential use with other hypomethylating agents, or switching to alternative treatments such as targeted therapies or clinical trials.

Azacitidine can show some benefit in TP53-mutated MDS and AML, but responses are often brief and overall outcomes are poor. Research is ongoing to improve results using combinations like azacitidine with APR-246 or venetoclax.

Azacitidine is primarily excreted renally, so caution is required in patients with renal impairment. Dose adjustments or closer monitoring may be necessary. In patients with severe hepatic dysfunction, use is generally avoided due to a higher risk of toxicity and lack of sufficient safety data.