Epigenetic mechanisms and next-gen editing platforms in hematology: From molecular basis to therapeutic frontiers.

Epigenetic regulation is fundamental to hematopoiesis, influencing stem cell fate, lineage commitment, and the development of hematologic diseases. Recent technological innovations have transitioned from traditional genetic editing towards programmable, reversible epigenetic modulation without altering the DNA sequence. This review explores the evolution of epigenetic editing platforms, from zinc finger proteins and TALEs to the transformative CRISPR-dCas9 system, and introduces next-generation technologies leveraging dCas12, dCas13, and modular RNA-guided systems. By fusing catalytically inactive CRISPR variants with chromatin or RNA-modifying enzymes, these tools enable precise control of gene expression and epitranscriptomic landscapes. In hematology, these advances offer novel strategies to modulate oncogenes, reactivate silenced tumor suppressors, and correct epigenetic dysregulation in malignancies such as leukemia, lymphoma, and myelodysplastic syndromes, as well as in inherited disorders like β-thalassemia and sickle cell disease. The integration of epigenetic editing into immune engineering, particularly in enhancing CAR-T and NK cell therapies, underscores its growing clinical impact. Together, these next-generation approaches herald a paradigm shift, enabling safer, more dynamic, and tunable interventions for blood disorders. This review highlights the current landscape and future directions of epigenetic editing, positioning it as a cornerstone of precision hematologic therapy.