Therapeutic potential of antisense oligonucleotides in hematological malignancies - 18/08/26
, Agathe Picard b , Elfie Perrudin a, Maria Oundjian a , Nina Tardif a , Anaïs Quemener a , Anne-Gaëlle RIO a , Marie-Dominique Galibert a, c , Virginie Gandemer a, b , Frédéric Mazurier a 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.
Le texte complet de cet article est disponible en PDF.Graphical Abstract |
Main genes targeted by ASOs tested in leukemia. Abl : Abelson kinase; AMP : adenosine monophosphate; ASO : antisense oligonucleotide; BAG3 : Bcl-2 associated athanogene 3; Bcl-2 : B-cell leukemia/lymphoma-2; BCR : B-cell receptor; BCR-ABL : BCR-ABL fusion protein; c-Myc : cellular myelocytomatosis; CREB : cyclic AMP response element-binding protein; E2A::PBX1 : transcription factor 3/PBX homeobox 1; FLT3-ITD: FLT3 gene internal tandem duplication; hTERT : human telomerase reverse transcriptase; KMT2A-AF4 ; lysine methyltransferase 2A-ALF transcription elongation factor 4; KMT2A-AF9 : lysine methyltransferase 2A-ALF transcription elongation factor 9; KMT2A-LTG19 : lysine methyltransferase 2A-leukemia translocation gene of chromosome 19; LnRNA PVT1 : long non-coding RNA plasmacytoma variant translocation 1; MDR1 : multidrug resistance 1; miR : micro ribonucleic acid; PML::RARalpha : promyelocytic leukemia/retinoic acid receptor-alpha; RNA : ribonucleic acid; S100A8 : S100 calcium binding protein A8; STAT : signal transducer and activator of transcription; TP53 : tumor protein 53; VEGF : vascular endothelial growth factor; WT1 : Wilms' tumor; XIAP : X-linked inhibitor of apoptosis protein.
Main genes targeted by ASOs tested in leukemia. Abl : Abelson kinase; AMP : adenosine monophosphate; ASO : antisense oligonucleotide; BAG3 : Bcl-2 associated athanogene 3; Bcl-2 : B-cell leukemia/lymphoma-2; BCR : B-cell receptor; BCR-ABL : BCR-ABL fusion protein; c-Myc : cellular myelocytomatosis; CREB : cyclic AMP response element-binding protein; E2A::PBX1 : transcription factor 3/PBX homeobox 1; FLT3-ITD: FLT3 gene internal tandem duplication; hTERT : human telomerase reverse transcriptase; KMT2A-AF4 ; lysine methyltransferase 2A-ALF transcription elongation factor 4; KMT2A-AF9 : lysine methyltransferase 2A-ALF transcription elongation factor 9; KMT2A-LTG19 : lysine methyltransferase 2A-leukemia translocation gene of chromosome 19; LnRNA PVT1 : long non-coding RNA plasmacytoma variant translocation 1; MDR1 : multidrug resistance 1; miR : micro ribonucleic acid; PML::RARalpha : promyelocytic leukemia/retinoic acid receptor-alpha; RNA : ribonucleic acid; S100A8 : S100 calcium binding protein A8; STAT : signal transducer and activator of transcription; TP53 : tumor protein 53; VEGF : vascular endothelial growth factor; WT1 : Wilms' tumor; XIAP : X-linked inhibitor of apoptosis protein. Le texte complet de cet article est disponible en PDF.
Keywords : Leukemia, Antisense oligonucleotides, Targeted therapy, RNA-based therapeutic, Personalized medicine, Drug delivery
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Vol 202
Article 119808- septembre 2026 Retour au numéro
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