Organ Systems, Bone Marrow, WHO Classification, MDS, MDS/MPN

SB3F1 Mutation

  • SB3F1 is a RNA splicesome, mutated SB3F1 may result in an alternative function proteins instead of a loss of function mutation (Obeng, et al.)  
  • Point mutations associated with MDS are in the regions of exons 14 to 16
  • ~25% of all cases of MDS have a SB3F1 mutation
  • ~80% of MDS-RS SLD have SBF3F1 mutation
  • 30-70% of MDS-RS MLD have SB3F1 mutation
  • 20% of MDS/MPN cases have SB3F1 mutation
  • Heterozygous mutation of SB3F1 mutation is associated with disease
  • Obeng et al. demonstrated in mice that an isolated SB3F1 mutation is sufficient to cause MDS-type findings
  • The presence of a SB3F1 mutation has a positive predictive value (PPV) of finding ring sideroblasts of 97.7%.

References
Obeng EA, Chappell RJ, Seiler M, Chen MC, Campagna DR, Schmidt PJ, et al. Physiologic Expression of Sf3b1(K700E) Causes Impaired Erythropoiesis, Aberrant Splicing, and Sensitivity to Therapeutic Spliceosome Modulation. Cancer Cell. 2016;30: 404–417. doi:10.1016/j.ccell.2016.08.006
 
Malcovati L, Karimi M, Papaemmanuil E, Ambaglio I, Jädersten M, Jansson M, et al. SF3B1 mutation identifies a distinct subset of myelodysplastic syndrome with ring sideroblasts. Blood. 2015;126: 233–241. doi:10.1182/blood-2015-03-633537
 
Swerdlow SH, Campo E, Harris, NL, Jaffe ES, Pileri SA, Stein H, Thiele J (Eds):  WHO Classification of Tumours of Haematopoietic and Lymphoid Tissues (Revised 4th edition). IARC: Lyon 2017