SF3B1 Mutations Negatively Predict for Response to Immunosuppressive Therapy in Myelodysplastic Syndromes

Clin Lymphoma Myeloma Leuk. 2020 Jun;20(6):400-406.e2. doi: 10.1016/j.clml.2019.12.023. Epub 2020 Jan 10.


Background: Immunosuppressive therapy (IST) yields durable hematologic improvement (HI) in a subset of patients with lower-risk myelodysplastic syndrome (MDS). Age, human leukocyte antigen (HLA)-DR15 positivity, and duration of transfusion dependence are putative clinical variables predictive for response. We investigated the effect of somatic gene mutations on response to IST in lower-risk MDS.

Patients and methods: Forty of 66 patients who received antithymocyte globulin with or without cyclosporine A identified at the Moffitt Cancer Center were molecularly profiled using a 49-gene myeloid panel. All patients profiled received antithymocyte globulin, and cyclosporine A was provided to 60% of patients.

Results: The overall frequency of HI was 42%. Presence of a large granular lymphocytic clone, hypocellular bone marrow, HLA-DR15 positivity, trisomy 8, and age had no influence on response to IST. Among 40 patients evaluated by next-generation sequencing, the presence of an SF3B1 mutation (MT) was significantly associated with IST nonresponse (1 of 9 SF3B1 MT, 11% vs. 21 of 31 wild type, 68%; P = .002). All patients with SF3B1 MT had ring sideroblasts > 15% (RS) by morphology; the corresponding HI rate was 20% among patients with RS versus 50% for those without RS (P = .09).

Conclusion: These findings support the clinical implementation of genomics in MDS. The presence of an SF3B1 mutation adversely influences response to IST and should be incorporated into treatment decisions upon validation of these findings.

Keywords: Antithymocyte globulin; Hematologic improvement; MDS; Response biomarkers; Somatic mutations.

Publication types

  • Clinical Trial
  • Multicenter Study

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Antilymphocyte Serum / administration & dosage*
  • Cyclosporine / administration & dosage*
  • Female
  • HLA-DR Serological Subtypes / genetics
  • HLA-DR Serological Subtypes / metabolism
  • Humans
  • Immunosuppressive Agents / administration & dosage*
  • Male
  • Middle Aged
  • Mutation*
  • Myelodysplastic Syndromes* / drug therapy
  • Myelodysplastic Syndromes* / genetics
  • Myelodysplastic Syndromes* / metabolism
  • Myelodysplastic Syndromes* / mortality
  • Phosphoproteins / genetics*
  • Phosphoproteins / metabolism
  • Predictive Value of Tests
  • RNA Splicing Factors / genetics*
  • RNA Splicing Factors / metabolism


  • Antilymphocyte Serum
  • HLA-DR Serological Subtypes
  • HLA-DR15 antigen
  • Immunosuppressive Agents
  • Phosphoproteins
  • RNA Splicing Factors
  • SF3B1 protein, human
  • Cyclosporine