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Genomic landscape of CD34 + hematopoietic cells in myelodysplastic syndrome and gene mutation profiles as prognostic markers
- Source :
- Proceedings of the National Academy of Sciences. 111:8589-8594
- Publication Year :
- 2014
- Publisher :
- Proceedings of the National Academy of Sciences, 2014.
-
Abstract
- Myelodysplastic syndrome (MDS) includes a group of diseases characterized by dysplasia of bone marrow myeloid lineages with ineffective hematopoiesis and frequent evolution to acute myeloid leukemia (AML). Whole-genome sequencing was performed in CD34(+) hematopoietic stem/progenitor cells (HSPCs) from eight cases of refractory anemia with excess blasts (RAEB), the high-risk subtype of MDS. The nucleotide substitution patterns were found similar to those reported in AML, and mutations of 96 protein-coding genes were identified. Clonal architecture analysis revealed the presence of subclones in six of eight cases, whereas mutation detection of CD34(+) versus CD34(-) cells revealed heterogeneity of HSPC expansion status. With 39 marker genes belonging to eight functional categories, mutations were analyzed in 196 MDS cases including mostly RAEB (n = 89) and refractory cytopenia with multilineage dysplasia (RCMD) (n = 95). At least one gene mutation was detected in 91.0% of RAEB, contrary to that in RCMD (55.8%), suggesting a higher mutational burden in the former group. Gene abnormality patterns differed between MDS and AML, with mutations of activated signaling molecules and NPM1 being rare, whereas those of spliceosome more common, in MDS. Finally, gene mutation profiles also bore prognostic value in terms of overall survival and progression free survival.
- Subjects :
- Male
NPM1
Myeloid
CD34
Antigens, CD34
Kaplan-Meier Estimate
Gene mutation
Biology
Somatic evolution in cancer
Clonal Evolution
hemic and lymphatic diseases
Biomarkers, Tumor
medicine
Humans
Cell Proliferation
Multidisciplinary
Genome, Human
Myelodysplastic syndromes
Myeloid leukemia
Cell Differentiation
Genomics
Sequence Analysis, DNA
Middle Aged
Biological Sciences
Hematopoietic Stem Cells
Prognosis
medicine.disease
medicine.anatomical_structure
Karyotyping
Myelodysplastic Syndromes
Multivariate Analysis
Mutation
Immunology
Cancer research
Female
Refractory cytopenia with multilineage dysplasia
Nucleophosmin
Subjects
Details
- ISSN :
- 10916490 and 00278424
- Volume :
- 111
- Database :
- OpenAIRE
- Journal :
- Proceedings of the National Academy of Sciences
- Accession number :
- edsair.doi.dedup.....6124461f1b7fc7dc74c5db750bbae8b3