Aptamers, which are intricate synthetic molecules composed of single-stranded DNA and RNA, have recently emerged as groundbreaking instruments in the complex and multifaceted realms of diagnosing and treating diverse and challenging cancers, particularly leukemia, a type of blood cancer characterized by the overproduction of abnormal white blood cells. These innovative chemical antibodies, celebrated for their remarkable cost-effectiveness, unparalleled sensitivity, and exceptional precision, provide a promising beacon of hope in the arena of oncology, a field that continuously seeks novel approaches to combat various malignancies. Aptamers are fundamentally transforming the landscape of personalized medicine by adeptly and specifically targeting aberrantly expressed biomarkers, effectively modulating critical signaling pathways, and significantly enhancing the efficacy of drug delivery systems, thereby optimizing therapeutic outcomes for patients. This comprehensive review meticulously highlights the recent advancements in aptamer-based technologies, showcasing their immense potential to refine prognostic models, enhance interventions guided by the presence of minimal residual disease, and broaden the therapeutic options available for patients suffering from high-risk or relapsed forms of leukemia. Nevertheless, in conjunction with their promising applications, this study also delves into an exploration of the myriad of challenges and obstacles that may impede the realization of their full clinical potential in the healthcare setting. Graphic abstract This schematic illustrates the multifaceted roles of aptamers in the context of leukemia. The Design segment outlines the SELEX-based selection and amplification process used to generate aptamer candidates from ssDNA/RNA libraries against target cells or proteins. The Diagnostic section highlights applications of aptamers conjugated with antibodies, nanoparticles, or fluorescent labels for precise detection of leukemia biomarkers. In the Therapeutic domain, aptamers are shown to enable targeted drug delivery, inhibit downstream signaling pathways, and recognize specific leukemia cells. Finally, the Challenges section addresses key translational barriers, including serum stability, renal clearance, safety, and overall performance limitations of aptamer-based systems.

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