Effects of Metformin on Leukemia: Biological Mechanisms, Targets, and Treatment Possibilities

Dana, Parisa; Deezagi, Abdolkhalegh

Volume 17, Issue 3 (September-2025 2025) Iranian Journal of Blood and Cancer 2025, 17(3): 35-45 | Back to browse issues page

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Dana P, Deezagi A. Effects of Metformin on Leukemia: Biological Mechanisms, Targets, and Treatment Possibilities. Iranian Journal of Blood and Cancer 2025; 17 (3) :35-45
URL: http://ijbc.ir/article-1-1794-en.html

Effects of Metformin on Leukemia: Biological Mechanisms, Targets, and Treatment Possibilities

Parisa Dana ^*¹

, Abdolkhalegh Deezagi²

1- Islamic Azad University،Science and Research Branch, Tehran, Iran. , parisadana95@gmail.com
2- National Institute of Genetic Engineering and Biotechnology, Tehran, Iran.

Abstract: (58 Views)

Metformin is a widely prescribed medication for managing diabetes, but it also affects cancer cell metabolism through both direct and indirect mechanisms. Cancer cells often divide rapidly, and this quick division, along with metabolic changes, increases intracellular free radicals and inhibits the enzyme hexokinase. This inhibition prevents the conversion of glucose to glucose-6-phosphate, leading to glucose deprivation and subsequently causing mitochondrial depolarization and apoptosis in cancer cells. KDM1A is an epigenetic regulator that plays a vital role in cancer development. Both KDM1A and metformin influence autophagy and cancer-related pathways, and their interaction could lead to new treatment strategies. Metformin reduces oxidative stress and activates ATM signaling, since the ATM gene encodes a tumor suppressor protein that helps repair DNA mutations during stress. Additionally, the drug enhances the recognition of damaged DNA by increasing ATM protein levels. In acute myeloid leukemia (AML), leukemic stem cells (LSCs) often develop resistance after chemotherapy, which greatly contributes to treatment failures. This article aims to explore how metformin affects LSCs, DNA repair gene expression, and related biological mechanisms, as well as its targets and therapeutic potential. This study reviews existing articles about metformin's mechanisms in leukemia. Metformin shows significant potential for reducing mortality rates associated with various cancers, including leukemia.

Keywords: Metformin, Leukemia, Metabolic changes, Mechanisms, KDM1A gene, ATM, Leukemia stem cells

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: Review Article | Subject: Adults Hematology & Oncology
Received: 2025/07/17 | Accepted: 2025/09/17 | Published: 2025/09/30

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