• What is SF3B1?
  • SF3B1 in Myelodysplastic Syndromes
  • SF3B1 Mutations
  • Clinical Trials

SF3B1

Splicing factor 3b, subunit 1, 155kDa (SF3B1) is a gene that codes for part of the splicing factor 3b protein complex (Gene 2014). The complex is a member of the spliceosome and is involved in transcription and mRNA processing (Gene 2014). Spliceosome mutations are observed in MDS, chronic lymphocytic leukemia (CLL), AML, and chronic myelomonocytic leukemia (CMML), and these mutations can cause abnormal expression patterns of some genes involved in cancer pathogenesis (Chesnais et al. 2012).​

Related Pathways

Contributors: Stephen A. Strickland, M.D., MSCI, Annette S. Kim, M.D., Ph.D.

Suggested Citation: Strickland, S., A. Kim. 2015. SF3B1. My Cancer Genome https://www.padiracinnovation.org/content/disease/myelodysplastic-syndromes/sf3b1/?tab=0 (Updated December 7).

Last Updated: December 7, 2015

SF3B1 in Myelodysplastic Syndromes

SF3B1 mutations occur in 19.9% of MDS (COSMIC). SF3B1 mutations are only observed in refractory anemia with ring sideroblasts (RARS), a type of MDS, and a subtype of MDS/MPN known as refractory anemia with ring sideroblasts and thrombocytosis (RARS-T; Cazzola, Della Porta, and Malcovati 2013). SF3B1 mutations are involved in ring sideroblast formation (Cazzola, Della Porta, and Malcovati 2013; Malcovati et al. 2011). Sideroblasts are red blood cell precursor cells, and ring sideroblasts are abnormal sideroblasts characterized by a ring of iron particles around the cell nucleus. SF3B1 contains a common K700E mutation as well as other recurrent mutations in homeodomains (Yoshida 2011), suggesting aberrant function of the gene.

SF3B1 mutations have been associated with favorable overall survival and a lower likelihood of transformation to AML (Cazzola, Della Porta, and Malcovati 2013; Malcovati et al. 2011).​

Contributors: Stephen A. Strickland, M.D., MSCI, Annette S. Kim, M.D., Ph.D.

Suggested Citation: Strickland, S., A. Kim. 2014. SF3B1 in Myelodysplastic Syndromes. My Cancer Genome https://www.padiracinnovation.org/content/disease/myelodysplastic-syndromes/sf3b1/ (Updated September 23).

Last Updated: September 23, 2014

SF3B1 Mutations in Myelodysplastic Syndromes

Properties
Location of mutations SF3B1 gene on 2q33.1
Frequency of SF3B1 mutations in MDS 19.9% (COSMIC)
Implications for Targeted Therapeutics
Response to bromodomain inhibitors, DOT1L inhibitors, or other targeted epigenetic therapies Unknown at this timea
Response to spliceosome-targeting therapies Unknown at this timeb
Response to Ras-targeting therapies Unknown at this timec

The most frequently mutated positions of SF3B1 are K700 (44.9%; COSMIC) and H662 (12.2%; COSMIC). SF3B1 mutations have been associated with favorable overall survival and a lower likelihood of transformation to AML (Cazzola, Della Porta, and Malcovati 2013; Malcovati et al. 2011).

a Bromodomain (BRD2, BRD3, BRD4, and BRDt) inhibitors and DOT1L inhibitors are in phase I studies in hematologic malignancies (Abdel-Wahab and Levine 2013). In addition, several other epigenetic targeted therapies, targeting IDH1/IDH2, EZH2, LSD1, or UTX/JMJD3, are in development (Abdel-Wahab and Levine 2013).

b Drugs targeting the spliceosome are in development; these drugs alter gene expression or affect alternative splicing in ways that inhibit cancer progression (Bonnal, Vigevani, and Valcarcel 2012).

c Efforts to develop Ras-targeting therapies are in progress and are hoped to be useful in hematologic malignancies (Ward, Braun, and Shannon 2012).

Contributors: Stephen A. Strickland, M.D., MSCI, Annette S. Kim, M.D., Ph.D.

Suggested Citation: Strickland, S., A. Kim. 2014. SF3B1 Mutations in Myelodysplastic Syndromes. My Cancer Genome https://www.padiracinnovation.org/content/disease/myelodysplastic-syndromes/sf3b1/327/ (Updated September 23).

Last Updated: September 23, 2014

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