SF3B1-mutated myelodysplastic syndrome (MDS) is a distinct disease subtype, with clinical implications for risk stratification, according to a proposal from the International Working Group for the Prognosis of Myelodysplastic Syndromes (IWG-PM) published in Blood.

While the World Health Organization (WHO) revised its classification of tumors of hematopoietic and lymphoid tissues in 2016, the only recognized MDS subtype remains MDS with isolated 5q deletion. As genomic profiling across oncology is rapidly improving, further subtype identification may improve risk stratification and treatment decision-making.

As a large proportion of patients with MDS have an SF3B1 mutation — the most common of somatic mutations in spliceosome genes in this patient population — the IWG-PM evaluated available evidence to determine whether SF3B1-mutated MDS should be recognized as a distinct disease subtype. Data from 3479 patients with known SF3B1 mutation status from 18 care centers or networks were used and 795 patients were found to have mutated SF3B1, while 2684 had SF3B1 wild-type.

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Based on their analyses, the authors recommended specific diagnostic criteria for SF3B1-mutated MDS, including:

  • Cytopenia, using standard values
  • Presence of a somatic SF3B1 mutation
  • Morphologic dysplasia, regardless of presence of ring sideroblasts
  • Bone marrow blasts less than 5%/peripheral blood blasts less than 1%
  • WHO criteria for MDS with isolated 5q deletion
  • Normal karyotype/any cytogenetic abnormality not including 5q deletion
  • Any somatic cell gene mutations other than RUNX1 or EZH2

Among the 495 patients identified in the evaluated patient group meeting these criteria, 57% were men, 48% were between ages 70 and 79 years, and 0% had a Revised International Prognostic Scoring System Cytogenetic Risk Group score of “poor” or “very poor,” with 84% considered “good.”

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The authors noted that SF3B1 mutations are almost always associated with MDS with ring sideroblasts among patients with clonal cytopenia of undetermined significance.

According to the proposal, treating SF3B1-mutated MDS as a distinct nosologic entity may help clinicians in risk stratification and treatment decision-making. The mutation is associated with a relatively good prognosis, may indicate a likely to response to luspatercept, and is possibly associated with a lack of needed transfusion.


Malcovati L, Stevenson K, Papaemmanuil E, et al. SF3B1-mutant myelodysplastic syndrome as a distinct disease subtype – a proposal of the International Working Group for the Prognosis of Myelodysplastic Syndromes (IWG-PM) [published online April 29, 2020]. Blood. doi: 10.1182/blood.2020004850