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

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

Research output: Contribution to journalArticlepeer-review

181 Scopus citations


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 MDSas 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 overtMDS 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. (Blood. 2020;136(2):157-170).

Original languageEnglish
Pages (from-to)157-170
Number of pages14
Issue number2
StatePublished - Jul 9 2020


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