{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T01:13:38Z","timestamp":1760058818781,"version":"build-2065373602"},"reference-count":48,"publisher":"MDPI AG","issue":"9","license":[{"start":{"date-parts":[[2025,5,3]],"date-time":"2025-05-03T00:00:00Z","timestamp":1746230400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Azelaic acid (AZA), an aliphatic dicarboxylic acid (HOOC-(CH2)7-COOH), is widely used in dermatology. It functions as an inhibitor of tyrosinase, mitochondrial respiratory chain enzymes, and DNA synthesis, while also scavenging free radicals and reducing reactive oxygen species (ROS) production by neutrophils. AZA has demonstrated anti-proliferative and cytotoxic effects on various cancer cells. However, its therapeutic potential in acute myeloid leukemia (AML) remains largely unexplored. AML is a complex hematologic malignancy characterized by the clonal transformation of hematopoietic precursor cells, involving chromosomal rearrangements and multiple gene mutations. The disease is associated with poor prognosis and high relapse rates, primarily due to its propensity to develop resistance to treatment. Recent studies indicate that AZA suppresses AML cell proliferation by inducing apoptosis and arresting the cell cycle at the G1 phase, with minimal cytotoxic effects on healthy cells. Additionally, AZA exerts antileukemic activity by modulating the ROS signaling pathway, enhancing the total antioxidant capacity in both AML cell lines and patient-derived cells. AZA also sensitizes AML cells to Ara-C chemotherapy. In vivo, AZA has been shown to reduce leukemic spleen infiltration and extend survival. As our understanding of AML biology progresses, the development of new molecularly targeted agents, in combination with traditional chemotherapy, offers the potential for improved treatment outcomes. This review aims to provide a comprehensive synthesis of preclinical evidence on the therapeutic potential of AZA in AML, consolidating current knowledge and identifying future directions for its clinical application.<\/jats:p>","DOI":"10.3390\/ijms26094362","type":"journal-article","created":{"date-parts":[[2025,5,4]],"date-time":"2025-05-04T20:10:27Z","timestamp":1746389427000},"page":"4362","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Harnessing Azelaic Acid for Acute Myeloid Leukemia Treatment: A Novel Approach to Overcoming Chemoresistance and Improving Outcomes"],"prefix":"10.3390","volume":"26","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-3730-1125","authenticated-orcid":false,"given":"Silvia","family":"Di Agostino","sequence":"first","affiliation":[{"name":"Department of Health Sciences, University Magna Graecia of Catanzaro, 88100 Catanzaroo, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8294-8684","authenticated-orcid":false,"given":"Anna","family":"Di Vito","sequence":"additional","affiliation":[{"name":"Department of Clinical and Experimental Medicine, University Magna Graecia of Catanzaro, 88100 Catanzaro, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Annamaria","family":"Aloisio","sequence":"additional","affiliation":[{"name":"Department of Medical and Surgical Sciences, University Magna Graecia of Catanzaro, 88100 Catanzaro, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Giovanna Lucia","family":"Piazzetta","sequence":"additional","affiliation":[{"name":"Department of Medical and Surgical Sciences, University Magna Graecia of Catanzaro, 88100 Catanzaro, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Nadia","family":"Lobello","sequence":"additional","affiliation":[{"name":"Department of Medical and Surgical Sciences, University Magna Graecia of Catanzaro, 88100 Catanzaro, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jessica","family":"Bria","sequence":"additional","affiliation":[{"name":"Department of Clinical and Experimental Medicine, University Magna Graecia of Catanzaro, 88100 Catanzaro, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8314-715X","authenticated-orcid":false,"given":"Emanuela","family":"Chiarella","sequence":"additional","affiliation":[{"name":"Department of Medical and Surgical Sciences, University Magna Graecia of Catanzaro, 88100 Catanzaro, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2025,5,3]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1345","DOI":"10.1182\/blood.2022016867","article-title":"Diagnosis and Management of AML in Adults: 2022 Recommendations from an International Expert Panel on Behalf of the ELN","volume":"140","author":"Wei","year":"2022","journal-title":"Blood"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"2073","DOI":"10.1016\/S0140-6736(23)00108-3","article-title":"Acute Myeloid Leukaemia","volume":"401","author":"DiNardo","year":"2023","journal-title":"Lancet"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"1119","DOI":"10.1182\/blood.2022018092","article-title":"Metabolism in Acute Myeloid Leukemia: Mechanistic Insights and Therapeutic Targets","volume":"141","author":"Mishra","year":"2023","journal-title":"Blood"},{"key":"ref_4","doi-asserted-by":"crossref","unstructured":"Pan, Y., Liu, D., Wei, Y., Su, D., Lu, C., Hu, Y., and Zhou, F. 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