SF3B1-mutant MDS as a distinct disease subtype: a proposal from the International Working Group for the Prognosis of MDS

Luca Malcovati (Lead / Corresponding author), Kristen E. Stevenson, Elli Papaemmanuil, Donna Neuberg, Rafael Bejar, Jacqueline Boultwood, David Bowen, Peter J. Campbell, Benjamin L. Ebert, Pierre Fenaux, Torsten Haferlach, Michael Heuser, Joop Jansen, Rami S. Komrokji, Jaroslaw P. Maciejewski, Matthew J. Walter, Michaela Fontenay, Guillermo Garcia-Manero, Timothy A. Graubert, Aly KarsanManja Meggendorfer, Andrea Pellagatti, David Sallman, Michael R. Savona, Mikkael A. Sekeres, David Steensma, Sudhir Tauro, Felicitas Thol, Paresh Vyas, Arjan A. Van De Loosdrecht, Detlef Haase, Heinz Tuechler, Peter L. Greenberg, Seishi Ogawa, Eva Hellström-Lindberg, Mario Cazzola

Research output: Contribution to journalArticlepeer-review

162 Citations (Scopus)
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The 2016 revision of the World Health Organization classification of tumors of hematopoietic and lymphoid tissues is characterized by a closer integration of morphology and molecular genetics. Notwithstanding, the myelodysplastic syndrome (MDS) with isolated del(5q) remains so far the only MDS subtype defined by a genetic abnormality. Approximately half of MDS patients carry somatic mutations in spliceosome genes, with SF3B1 being the most commonly mutated one. SF3B1 mutation identifies a condition characterized by ring sideroblasts (RS), ineffective erythropoiesis, and indolent clinical course. A large body of evidence supports recognition of SF3B1-mutant MDS as a distinct nosologic entity. To further validate this notion, we interrogated the data set of the International Working Group for the Prognosis of MDS (IWG-PM). Based on the findings of our analyses, we propose the following diagnostic criteria for SF3B1-mutant MDS: (1) cytopenia as defined by standard hematologic values, (2) somatic SF3B1 mutation, (3) morphologic dysplasia (with or without RS), and (4) bone marrow blasts <5% and peripheral blood blasts <1%. Selected concomitant genetic lesions represent exclusion criteria for the proposed entity. In patients with clonal cytopenia of undetermined significance, SF3B1 mutation is almost invariably associated with subsequent development of overt MDS with RS, suggesting that this genetic lesion might provide presumptive evidence of MDS in the setting of persistent unexplained cytopenia. Diagnosis of SF3B1-mutant MDS has considerable clinical implications in terms of risk stratification and therapeutic decision making. In fact, this condition has a relatively good prognosis and may respond to luspatercept with abolishment of the transfusion requirement.

Original languageEnglish
Pages (from-to)157-170
Number of pages14
Issue number2
Early online date29 Apr 2020
Publication statusPublished - 9 Jul 2020


  • mutation
  • sf3b1 gene
  • myelodysplastic syndrome

ASJC Scopus subject areas

  • Biochemistry
  • Immunology
  • Hematology
  • Cell Biology


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