SRSF2

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Serine/arginine-rich splicing factor 2 (Protein PR264) (Splicing component, 35 kDa) (Splicing factor SC35) (SC-35) (Splicing factor, arginine/serine-rich 2) [SFRS2]

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Insight into the molecular pathophysiology of myelodysplastic syndromes: targets for novel therapy.

Myelodysplastic syndromes (MDS) are clonal hematopoietic stem cell disorders characterized by abnormal cellular differentiation and maturation with variable progression to acute leukemia. Over the last decade, scientific discoveries have unraveled specific pathways involved in the complex pathophysiology of MDS. Prominent examples include aberrations in cytokines and their signaling pathways (such as tumor necrosis factor-alpha, interferon-gamma, SMAD proteins), mutations in genes encoding the RNA splicing machinery (SF3B1, SRSF2, ZRSR2, and U2AF1 genes), mutations in genes disrupting the epigenetic machinery (TET2, DNMT3A, DNMT3B, EZH2, ASXL1). In addition, abnormalities in regulatory T-cell dynamics and atypical interactions between the bone marrow microenvironment, stroma and progenitor cells, and abnormal maintenance of telomeres are also notable contributors to the complex pathogenesis of MDS. These pathways represent potential targets for novel therapies. Specific therapies include drugs targeting aberrant DNA methylation and chromatin remodeling, modulating/activating the immune system to enhance tumor-specific cellular immune responses and reduce anomalous cytokine signaling, and blocking abnormal interaction between hematopoietic progenitors and stromal cells.

MeSH Terms

  • Animals
  • Bone Marrow
  • Cellular Microenvironment
  • Cellular Senescence
  • Cytokines
  • DNA Methylation
  • Epigenesis, Genetic
  • Gene Expression Regulation
  • Gene Silencing
  • Genetic Variation
  • Humans
  • Immune System Diseases
  • Molecular Targeted Therapy
  • Myelodysplastic Syndromes
  • RNA Splicing
  • Signal Transduction
  • Stromal Cells
  • Telomere

Keywords

  • bone marrow microenvironment
  • cellular senescence
  • cytokines
  • epigenetic regulation
  • immune dysregulation
  • myelodysplastic syndromes
  • pathogenesis
  • targeted therapies
  • telomeric erosion