The genetic basis of myelodysplasia and its clinical relevance

Research output: Contribution to journalArticle

187 Citations (Scopus)

Abstract

Myelodysplasia is a diagnostic feature of myelodysplastic syndromes (MDSs) but is also found in other myeloid neoplasms. Its molecular basis has been recently elucidated by means of massive parallel sequencing studies. About 90% of MDS patients carry ge;1 oncogenic mutations, and two thirds of them are found in individuals with a normal karyotype. Driver mutant genes include those of RNA splicing (SF3B1, SRSF2, U2AF1, and ZRSR2), DNA methylation (TET2, DNMT3A, and IDH1/2), chromatin modification (ASXL1 and EZH2), transcription regulation (RUNX1), DNA repair (TP53), signal transduction (CBL, NRAS, and KRAS), and cohesin complex (STAG2). Only 4 to 6 genes are consistently mutated in ge;10% MDS patients, whereas a long tail of ~50 genes are mutated less frequently. At presentation, most patients typically have 2 or 3 driver oncogenic mutations and hundreds of background mutations. MDS driver genes are also frequently mutated in other myeloid neoplasms. Reliable genotype/phenotype relationships include the association of the SF3B1 mutation with refractory anemia with ring sideroblasts, TET2/SRSF2 comutation with chronic myelomonocytic leukemia, and activating CSF3R mutation with chronic neutrophilic leukemia. Although both founding and subclonal driver mutations have been shown to have prognostic significance, prospective clinical trials that include the molecular characterization of the patient's genome are now needed.

Original languageEnglish
Pages (from-to)4021-4034
Number of pages14
JournalBlood
Volume122
Issue number25
DOIs
Publication statusPublished - Dec 12 2013

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Genes
Myelodysplastic Syndromes
Mutation
Leukemia, Neutrophilic, Chronic
Signal transduction
Leukemia, Myelomonocytic, Chronic
Refractory Anemia
RNA Splicing
Transcription
Refractory materials
Chromatin
DNA Methylation
Karyotype
Repair
DNA Repair
Association reactions
RNA
Signal Transduction
Neoplasms
Genotype

ASJC Scopus subject areas

  • Hematology
  • Biochemistry
  • Cell Biology
  • Immunology

Cite this

The genetic basis of myelodysplasia and its clinical relevance. / Cazzola, Mario; Della Porta, Matteo G.; Malcovati, Luca.

In: Blood, Vol. 122, No. 25, 12.12.2013, p. 4021-4034.

Research output: Contribution to journalArticle

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