Biologic and clinical significance of somatic mutations of SF3B1 in myeloid and lymphoid neoplasms

Mario Cazzola, Marianna Rossi and Luca Malcovati


Precursor mRNA splicing is catalyzed by the spliceosome, a macromolecule composed of small nuclear RNAs associated with proteins. The SF3B1 gene encodes subunit 1 of the splicing factor 3b, which is important for anchoring the spliceosome to precursor mRNA. In 2011, whole exome sequencing studies showed recurrent somatic mutations of SF3B1 and other genes of the RNA splicing machinery in patients with myelodysplastic syndrome or myelodysplastic/myeloproliferative neoplasm. SF3B1 mutations had a particularly high frequency among conditions characterized by ring sideroblasts, consistent with a causal relationship. SF3B1 mutants were detected at lower frequency also in a variety of other tumor types. In chronic lymphocytic leukemia, SF3B1 was found to be the second most frequently mutated gene. In myelodysplastic syndromes, SF3B1 mutations appear to be founding genetic lesions and are associated with a low risk of leukemic evolution. By contrast, SF3B1 mutations have a lower incidence in early stages of chronic lymphocytic leukemia, are more common in advanced disease, and tend to be associated with poor prognosis, suggesting that they occur during clonal evolution of the disease. In perspective, assessment of SF3B1 mutation status may become part of innovative diagnostic and prognostic tools, while the availability of spliceosome modulators opens novel therapeutic prospects.

  • Submitted September 7, 2012.
  • Accepted October 31, 2012.