Driver somatic mutations identify distinct disease entities within myeloid neoplasms with myelodysplasia

Luca Malcovati, Elli Papaemmanuil, Ilaria Ambaglio, Chiara Elena, Anna Gallì, Matteo G. Della Porta, Erica Travaglino, Daniela Pietra, Cristiana Pascutto, Marta Ubezio, Elisa Bono, Matteo C. Da Vià, Angela Brisci, Francesca Bruno, Laura Cremonesi, Maurizio Ferrari, Emanuela Boveri, Rosangela Invernizzi, Peter J. Campbell, Mario Cazzola

Research output: Contribution to journalArticlepeer-review


Our knowledge of the genetic basis of myelodysplastic syndromes (MDS) and myelodysplastic/myeloproliferative neoplasms (MDS/MPN) has considerably improved. Todefine genotype/phenotype relationships of clinical relevance,westudied 308 patients with MDS, MDS/MPN, or acute myeloid leukemia evolving from MDS. Unsupervised statistical analysis, including the World Health Organization classification criteria and somatic mutations, showed that MDS associated with SF3B1-mutation (51 of 245 patients, 20.8%) is a distinct nosologic entity irrespective of current morphologic classification criteria. Conversely, MDS with ring sideroblasts with nonmutated SF3B1 segregated in different clusters with otherMDS subtypes. Mutations of genes involved in DNA methylation, splicing factors other than SF3B1, and genes of the RAS pathway and cohesin complex were independently associated with multilineage dysplasia and identified a distinct subset (51 of 245 patients, 20.8%). No recurrent mutation pattern correlated with unilineage dysplasia without ring sideroblasts. Irrespective of driver somatic mutations, a threshold of 5% bone marrow blasts retained a significant discriminant value for identifying cases with clonal evolution.Comutation of TET2 and SRSF2 was highly predictive of a myeloid neoplasm characterized by myelodysplasia and monocytosis, including but not limited to, chronic myelomonocytic leukemia. These results serve as a proof of concept that a molecular classification of myeloid neoplasms is feasible.

Original languageEnglish
Pages (from-to)1513-1521
Number of pages9
Issue number9
Publication statusPublished - Aug 28 2014

ASJC Scopus subject areas

  • Hematology
  • Biochemistry
  • Cell Biology
  • Immunology


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