RBPs in Hematopoietic Stem Cell Maintenance and Leukemia Initiation: Critical Gaps

Context RNA-binding proteins (RBPs) are key regulators of post-transcriptional gene expression and play essential roles in hematopoietic stem cell (HSC) function. Although major advances have been made in understanding transcriptional regulation in hematopoiesis, the contribution of RBPs to HSC maintenance and leukemia development remains incompletely defined. Evidence Acquisition Relevant literature was collected from major scientific databases and high-impact journals, including PubMed, Web of Science, Google Scholar, Nature Portfolio, Elsevier, and related peer-reviewed sources. This systematic review summarizes current findings on the roles of major RBPs and RNA-modifying factors in normal and malignant hematopoiesis, with particular focus on MUSASHI2, IGF2BP family proteins, Lin28b, METTL3, METTL14, ALKBH5, and FTO. Results Available studies demonstrate that RBPs regulate RNA processing, stability, translation, and modification, thereby influencing stem cell self-renewal, differentiation, and leukemic transformation. Dysregulation of these factors contributes to leukemia progression, maintenance of leukemia stem cells, and treatment resistance. Emerging evidence also highlights RBP-associated pathways as potential therapeutic targets. Conclusion RBPs represent a critical regulatory layer in hematopoietic stem cell biology and leukemia. Improved understanding of these post-transcriptional mechanisms may support the development of more effective therapies that target leukemia stem cells while preserving normal hematopoiesis.