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Driver somatic mutations identify distinct disease entities within myeloid neoplasms with myelodysplasia
- Source :
- Blood. 124:1513-1521
- Publication Year :
- 2014
- Publisher :
- American Society of Hematology, 2014.
-
Abstract
- Our knowledge of the genetic basis of myelodysplastic syndromes (MDS) and myelodysplastic/myeloproliferative neoplasms (MDS/MPN) has considerably improved. To define genotype/phenotype relationships of clinical relevance, we studied 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 other MDS 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.
- Subjects :
- Adult
Male
Myeloid
Cohesin complex
Chromosomal Proteins, Non-Histone
Immunology
Chronic myelomonocytic leukemia
Cell Cycle Proteins
Biology
Biochemistry
Somatic evolution in cancer
Myeloid Neoplasm
Cohort Studies
Myelodysplastic–myeloproliferative diseases
hemic and lymphatic diseases
medicine
Humans
Myeloid Cells
Genetic Association Studies
Aged
Aged, 80 and over
Myeloid Neoplasia
Myelodysplastic syndromes
Myeloid leukemia
Cell Biology
Hematology
DNA Methylation
Middle Aged
Ribonucleoprotein, U2 Small Nuclear
Phosphoproteins
Prognosis
medicine.disease
Myelodysplastic-Myeloproliferative Diseases
Leukemia, Myeloid, Acute
Genes, ras
medicine.anatomical_structure
Hematologic Neoplasms
Myelodysplastic Syndromes
Core Binding Factor Alpha 2 Subunit
Mutation
Cancer research
Female
RNA Splicing Factors
human activities
Subjects
Details
- ISSN :
- 15280020 and 00064971
- Volume :
- 124
- Database :
- OpenAIRE
- Journal :
- Blood
- Accession number :
- edsair.doi.dedup.....307ac49a399895bb6220c9e6184d6818