Gene affected:
SF3B1 - Splicing Factor 3b Subunit 1

Clinical significance
SF3B1 is strongly associated with ring sideroblasts in the bone marrow, and this knowledge has led to changes to the WHO Classification for Haematological Malignancy diagnostic criteria for Myelodysplasia with Ring Sideroblasts (MDS-RS). Splicing inhibitors are in early clinical trials including a specific SF3B1 inhibitor.

SF3B1image.jpg Ringed sideroblasts in SF3B1 mutated MDS (Perls stain)

Function of gene

SF3B1 forms part of the spliceosome complex and is involved in transcription and mRNA processing. Spliceosome mutations are thought to promote malignancy through missplicing of genes involved in epigenetic regulation, transcription, and genome integrity.

NGS panel gene coverage

Exons 13-16


MDS (20%)
Strongly associated with the MDS-RS subtype (~80% cases) and is associated with a favourable outcome with a low risk of transformation to AML. If the SF3B1 mutation is present then the percentage of ring sideroblasts required for diagnosis reduces from 15% to 5%.
AML (<5%)
Generally associated with other mutations, therefore difficult to assess the prognostic implication of SF3B1 alone
MDS/MPN-RS-T (MDS/MPN with Ring Sideroblasts and Thrombocytosis (>80%)
Associated with a favourable outcome and low risk of AML transformation. 15% ring sideroblasts on bone marrow still required for diagnosis irrespective of SF3B1 mutation status
MF (1~6%)
No recognised survival influence
CHIP (Clonal Haematopoiesis of Indeterminate Prognosis) (!3%)

Context: Mutations in SF3B1 are strongly associated with JAK2 mutations in MDS/MPD-RS-T and MFS. They also have associations with CALR and MPL less frequently in these disorders.


GeneWiki link:
Gene Wiki entry for SF3B1

1. SF3B1 in MDS subtypes

2. SF3B1 in MDS/MPD