# Harnessing Azelaic Acid for Acute Myeloid Leukemia Treatment: A Novel Approach to Overcoming Chemoresistance and Improving Outcomes

## TL;DR

Azelaic acid shows promise in treating acute myeloid leukemia by reducing chemoresistance and improving survival in preclinical studies.

## Contribution

This paper reviews the novel therapeutic potential of azelaic acid in overcoming AML chemoresistance and enhancing treatment outcomes.

## Key findings

- AZA induces apoptosis and G1 cell cycle arrest in AML cells with minimal toxicity to healthy cells.
- AZA modulates ROS signaling and enhances antioxidant capacity in AML cell lines and patient-derived cells.
- AZA sensitizes AML cells to Ara-C chemotherapy and reduces leukemic spleen infiltration in vivo.

## Abstract

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.