Therapeutic strategies targeting aberrant RNA splicing in myeloid malignancies Review
| Authors: | Boussi, L.; Biswas, J.; Abdel-Wahab, O.; Stein, E. |
| Review Title: | Therapeutic strategies targeting aberrant RNA splicing in myeloid malignancies |
| Abstract: | In recent years, large-scale sequencing efforts have identified targetable driver mutations in haematopoietic stem cells. These efforts have led to the development and approval of nine novel agents for relapsed or refractory acute myelogenous leukaemia (R/R AML). However, despite an expansion in targeted therapies, achieving a durable remission in AML and high-risk myelodysplastic syndrome (HR-MDS) remains a significant challenge, and there is an urgent need for new effective treatments. Modulation of aberrant RNA splicing has emerged as a novel therapeutic approach in myeloid diseases. Aberrant splicing drives dysregulated gene expression that promotes tumourigenesis through increased proliferation and metastatic potential, immune evasion, decreased apoptosis, and chemotherapy resistance. Mutations in spliceosomal components have been identified in numerous cancer subtypes, with mutations in RNA binding proteins SF3B1, SRSF2, U2AF1, and ZRSR2 occurring frequently in AML and in up to 60% of patients with MDS, as well as in chronic myelomonocytic leukaemia and in 10% of patients with chronic lymphocytic leukaemia. In this review, we explore therapeutic strategies targeting aberrant splicing and the potential of these approaches to drive clinical responses. © 2024 British Society for Haematology and John Wiley & Sons Ltd. |
| Keywords: | chronic myelomonocytic leukemia; human cell; genetics; mutation; leukemia, myeloid, acute; review; antineoplastic agents; antineoplastic agent; metabolism; apoptosis; gene expression; carcinogenesis; rna binding protein; acute leukemia; myelodysplastic syndrome; drug combination; remission; hematopoietic stem cell; spliceosome; drug therapy; chronic lymphatic leukemia; therapy; clinical trials; rna splicing; myelodysplastic syndromes; mds; molecularly targeted therapy; immune evasion; molecular targeted therapy; acute myeloid leukemia; spliceosomes; acute leukaemia; humans; human; rna splicing factor; rna splicing factors; neoplastic cell transformation |
| Journal Title: | British Journal of Haematology |
| Volume: | 205 |
| Issue: | 6 |
| ISSN: | 0007-1048 |
| Publisher: | John Wiley & Sons |
| Date Published: | 2024-12-01 |
| Start Page: | 2153 |
| End Page: | 2162 |
| Language: | English |
| DOI: | 10.1111/bjh.19826 |
| PUBMED: | 39406457 |
| PROVIDER: | scopus |
| DOI/URL: | |
| Notes: | Review -- Source: Scopus |
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