IWG-PM Publishes Proposed Diagnostic Criteria for SF3B1-Mutant MDS

The International Working Group for the Prognosis of MDS (IWG-PM) has published a proposal for new diagnostic criteria for SF3B1-mutant myelodysplastic syndromes (MDS) as a distinct disease subtype. The proposed diagnostic criteria, which the working group says may improve risk stratification and therapeutic decision-making, were published in Blood.

When asked about how this proposal may affect clinical care or future research, study author Luca Malcovati, MD, of the University of Pavia in Italy, told ASH Clinical News, “The proposed diagnostic criteria identify a disease entity with a homogeneous molecular basis and characteristic clinical features, which will support tailored management and therapeutic strategies and clinical trials aimed at developing specific treatments targeting aberrant splicing and its functional consequences.”

To develop the criteria, the IWG-PM performed an analysis of available evidence that supported the recognition of SF3B1-mutant MDS as a distinct nosologic entity. The analysis looked at a data set of the IWG-PM database, which included a total of 3,479 patients with a known SF3B1 mutation status from 18 medical centers or networks.

Currently, MDS are categorized by the World Health Organization (WHO) based on the number of hematopoietic lineages manifesting dysplasia, bone marrow and blood blast proportion, karyotype (in the case of del(5q) MDS), exposure history, and the presence and proportion of ring sideroblasts. SF3B1 somatic mutations are closely associated with ring sideroblast morphology, and the WHO classification includes SF3B1 mutation status as a supplementary criterion for defining MDS with ring sideroblasts.

The working group cited research that suggests SF3B1 mutations feature a positive prognostic value for overall survival and risk of disease progression. The IWG-PM data set confirmed previous reports that an SF3B1 mutation identified patients with MDS who had a favorable prognosis.

The IWG-PM data set was also used to examine the prognostic value of cytogenetic abnormalities in the context of SF3B1-mutant MDS and researchers observed no significant effect in outcomes depending on the absence or presence of del(5q). The investigators also found that in the context of SF3B1 mutation, a restricted spectrum of subclonal mutations drive clonal progression.

In addition, 20% of patients with WHO-classified MDS with ring sideroblasts (MDS-RS) do not harbor the SF3B1 mutation. However, current evidence suggests SF3B1-unmutated MDS-RS differs from SF3B1-mutated MDS, including a higher prevalence of myeloid and megakaryocyte dysplasia and poorer survival. This was confirmed from an analysis of the IWG data set.

The IWG-PM proposed the following diagnostic criteria for MDS with mutated SF3B1:

  • at least one cytopenia, as defined by standard hematologic values
  • somatic SF3B1 mutation
  • morphologic dysplasia, with or without ring sideroblasts
  • bone marrow blasts <5% and peripheral blood blasts <1%
  • exclusion of WHO criteria for MDS with isolated del(5q), MDS/myeloproliferative neoplasm with ring sideroblasts and thrombocytosis (MDS/MPN-RS-T) or other MDS/MPN

The authors noted that minimal variant allele frequency for the SF3B1 mutation should be better defined in future studies. Additional investigation is warranted on the effect of varying SF3B1 alleles on clinical phenotype and disease outcome in SF3B1-mutant MDS.

The authors report no relevant conflicts of interest.


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). 2020 Apr 29. Blood. [Epub ahead of print]