Splicing dysregulation in human hematologic malignancies: beyond splicing mutations.

Area of Science:

• Molecular Biology
• Cancer Research
• Genetics

Background:

• Alternative splicing (AS) enhances proteome diversity but its dysregulation drives oncogenesis.
• Spliceosome mutations (SMs) are implicated in hematologic diseases, but other factors also contribute.
• Post-translational modifications (PTMs), transcriptional alterations of splicing factors (SFs), and epigenetic signatures impact splicing.

Purpose of the Study:

• To provide an overview of emerging mechanisms contributing to aberrant splicing in cancer.
• To discuss the clinical potential of targeting aberrant splicing pathways.
• To highlight the role of aberrant splicing in the neoantigen repertoire of cancers.

Main Methods:

• Literature review of recent findings on splicing dysregulation.
• Analysis of the contribution of PTMs, transcriptional alterations, and epigenetic signatures.
• Examination of the link between aberrant splicing and cancer neoantigens.

Main Results:

• Aberrant splicing is a significant factor in oncogenesis, particularly in hematologic malignancies.
• Mechanisms beyond spliceosome mutations, including PTMs and epigenetic changes, are crucial.
• Aberrant splicing influences the cancer neoantigen landscape.

Conclusions:

• Emerging mechanisms of aberrant splicing present novel therapeutic targets for blood cancers.
• Targeting splicing dysregulation holds promise for developing innovative cancer treatments.
• Further research into splicing alterations can lead to improved cancer therapies.