Splice factor mutations and alternative splicing as drivers of hematopoietic malignancy

Immunol Rev. 2015 Jan;263(1):257-78. doi: 10.1111/imr.12241.

Abstract

Differential splicing contributes to the vast complexity of mRNA transcripts and protein isoforms that are necessary for cellular homeostasis and response to developmental cues and external signals. The hematopoietic system provides an exquisite example of this. Recently, discovery of mutations in components of the spliceosome in various hematopoietic malignancies (HMs) has led to an explosion in knowledge of the role of splicing and splice factors in HMs and other cancers. A better understanding of the mechanisms by which alternative splicing and aberrant splicing contributes to the leukemogenic process will enable more efficacious targeted approaches to tackle these often difficult to treat diseases. The clinical implications are only just starting to be realized with novel drug targets and therapeutic strategies open to exploitation for patient benefit.

Keywords: alternative splicing; hematopoiesis; hematopoietic malignancy; leukemogenesis; splice factors.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Alternative Splicing / genetics*
  • Animals
  • Carcinogenesis / genetics
  • Hematologic Neoplasms / drug therapy
  • Hematologic Neoplasms / genetics*
  • Humans
  • Molecular Targeted Therapy
  • Mutation / genetics
  • Nuclear Proteins / genetics*
  • Phosphoproteins / genetics*
  • Protein Isoforms / genetics
  • Protein Isoforms / metabolism
  • RNA Splice Sites / genetics
  • RNA Splicing Factors
  • RNA, Messenger / genetics*
  • Ribonucleoprotein, U2 Small Nuclear / genetics*
  • Ribonucleoproteins / genetics*
  • Serine-Arginine Splicing Factors
  • Splicing Factor U2AF

Substances

  • Nuclear Proteins
  • Phosphoproteins
  • Protein Isoforms
  • RNA Splice Sites
  • RNA Splicing Factors
  • RNA, Messenger
  • Ribonucleoprotein, U2 Small Nuclear
  • Ribonucleoproteins
  • SF3B1 protein, human
  • Splicing Factor U2AF
  • U2AF1 protein, human
  • SRSF2 protein, human
  • Serine-Arginine Splicing Factors