Biological relevance of alternative splicing in hematologic malignancies.
Monika WlodarczykKrzysztof GiannopoulosPublished in: Molecular medicine (Cambridge, Mass.) (2024)
Alternative splicing (AS) is a strictly regulated process that generates multiple mRNA variants from a single gene, thus contributing to proteome diversity. Transcriptome-wide sequencing studies revealed networks of functionally coordinated splicing events, which produce isoforms with distinct or even opposing functions. To date, several mechanisms of AS are deregulated in leukemic cells, mainly due to mutations in splicing and/or epigenetic regulators and altered expression of splicing factors (SFs). In this review, we discuss aberrant splicing events induced by mutations affecting SFs (SF3B1, U2AF1, SRSR2, and ZRSR2), spliceosome components (PRPF8, LUC7L2, DDX41, and HNRNPH1), and epigenetic modulators (IDH1 and IDH2). Finally, we provide an extensive overview of the biological relevance of aberrant isoforms of genes involved in the regulation of apoptosis (e. g. BCL-X, MCL-1, FAS, and c-FLIP), activation of key cellular signaling pathways (CASP8, MAP3K7, and NOTCH2), and cell metabolism (PKM).
Keyphrases
- single cell
- cell cycle arrest
- induced apoptosis
- gene expression
- dna methylation
- rna seq
- signaling pathway
- copy number
- genome wide
- transcription factor
- low grade
- oxidative stress
- endoplasmic reticulum stress
- pi k akt
- small molecule
- poor prognosis
- binding protein
- cell proliferation
- acute myeloid leukemia
- atrial fibrillation
- cell therapy
- wild type
- stem cells
- bone marrow
- epithelial mesenchymal transition
- mesenchymal stem cells
- high grade