Therapeutic potential of antisense oligonucleotides in hematological malignancies.

Abstract

Antisense oligonucleotides (ASOs) are short synthetic oligonucleotides composed of DNA, RNA, or chemically modified nucleotides, that represent a promising class of therapeutics for personalized medicine. This review synthesizes the clinical evidence from published studies evaluating ASOs in myelodysplastic syndromes, acute myeloid leukemia, acute lymphoblastic leukemia and chronic lymphocytic leukemia. Preclinical investigations and early-phase clinical trials have yielded encouraging results, demonstrating manageable toxicity profiles and supporting ongoing phase II and III evaluations. Although definitive clinical efficacy in leukemia has yet to be established, advances in target identification and continuous technological innovations, highlighted in this review, are progressively overcoming pharmacological, toxicological, and formulation challenges. ASO-based therapies may thus offer a highly versatile and rapidly adaptable platform for precision medicine in leukemia. Future progress will depend on rigorous translational studies addressing delivery efficiency and off-target effects, as well as on clinical trials designed to identify optimal combination strategies. With these developments, ASOs hold the potential to become a cornerstone of next-generation, highly personalized therapies, offering renewed hope to patients with limited treatment options and establishing a paradigm for precision-targeted interventions in leukemias.