Genetics of myelodysplastic syndromes: new insights.

@article{Graubert2011GeneticsOM,
  title={Genetics of myelodysplastic syndromes: new insights.},
  author={Timothy A. Graubert and Matthew J. Walter},
  journal={Hematology. American Society of Hematology. Education Program},
  year={2011},
  volume={2011},
  pages={
          543-9
        }
}
  • T. Graubert, M. Walter
  • Published 10 December 2011
  • Biology, Medicine
  • Hematology. American Society of Hematology. Education Program
Myelodysplastic syndromes (MDS) are a heterogenous group of hematologic malignancies characterized by clonal expansion of BM myeloid cells with impaired differentiation. The identification of recurrent mutations in MDS samples has led to new insights into the pathophysiology of these disorders. Of particular interest is the recent recognition that genes involved in the regulation of histone function (EZH2, ASXL1, and UTX) and DNA methylation (DNMT3A, IDH1/IDH2, and TET2) are recurrently mutated… 
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Genetics factors associated with myelodysplastic syndromes.
The molecular pathogenesis of the myelodysplastic syndromes
TLDR
It is now recognized that haploinsufficiency (a gene dosage effect) resulting from gene deletions or inactivating mutations is an important disease mechanism in MDS.
The molecular basis and clinical significance of genetic mutations identified in myelodysplastic syndromes.
Molecular Pathogenesis of Myelodysplastic Syndromes
TLDR
The molecular abnormalities in key relevant components of the biology and pathogenesis of MDS are summarized and an update on the clinical impact and therapeutic response in MDS patients is provided.
Molecular Genetics of Myelodysplastic Syndromes
TLDR
The particular combination of somatic genetic lesions in any given patient will influence how their disease is manifested, and together with individual background germline genotype may explain much of the clinical heterogeneity associated with MDS.
Molecular genetic methods in the diagnosis of myelodysplastic syndromes. A review.
TLDR
This review focuses on the advantages, limitations, clinical applications and future perspectives of three molecular methods currently used in genetic testing and/ or translational research of MDS.
Myelodysplastic syndrome: an inability to appropriately respond to damaged DNA?
[Myelodysplastic syndromes. Epidemiology, molecular and morphological characteristics and risk stratification].
TLDR
Mutations affecting growth factor receptors, cell cycle and apoptosis regulators, intracellular signaling, transcription factors, epigenetic regulation and the splicosome are involved in MDS pathogenesis and progression.
Recent advances in myelodysplasia: update from 2011 ASH annual meeting
  • Delong Liu
  • Biology, Medicine
    Journal of Hematology & Oncology
  • 2012
TLDR
Significant progresses have been made in genetic research in MDS, and mutations of DNMT3A, IDH1/2, and TET2 were found to be correlated with responses to azacytidine /decitabine, and microRNA-21 may also serve as a biomarker for therapy response to hypomethylating agents in M DS.
TP53 in Myelodysplastic Syndromes: Recent Biological and Clinical Findings
TLDR
The recent biological and clinical findings of TP53-mutated MDS are reported, focusing on the molecular pathways activation and on its impact on the cellular physiology.
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References

SHOWING 1-10 OF 58 REFERENCES
Unraveling the molecular pathophysiology of myelodysplastic syndromes.
  • R. Bejar, R. Levine, B. Ebert
  • Biology, Medicine
    Journal of clinical oncology : official journal of the American Society of Clinical Oncology
  • 2011
TLDR
Elucidation of the full complement of genetic causes of MDS promises profound insight into the biology of the disease, improved classification and prognostic scoring schemes, and the potential for novel targeted therapies with molecular predictors of response.
Mutations of polycomb‐associated gene ASXL1 in myelodysplastic syndromes and chronic myelomonocytic leukaemia
TLDR
The results show that ASXL1 might play the role of a tumour suppressor in myeloid malignancies, a disease classified as MDS/Myeloproliferative disorder.
Acquired mutations in TET2 are common in myelodysplastic syndromes
TLDR
It is concluded that TET2 is the most frequently mutated gene in MDS known so far, and expression was shown to be elevated in hematopoietic cells with highest expression in granulocytes, in line with a function in myelopoiesis.
Updates in Cytogenetics and Molecular Markers in MDS
TLDR
An update on the changing landscape of molecular and cytogenetic characterization in MDS and its significance in disease biology and clinical practice is provided.
Mutational Spectrum In Chronic Myelomonocytic Leukemia Includes Genes Associated with Epigenetic Regulation Such as UTX and EZH2
TLDR
Results of broad molecular screen in a group of 63 patients with CMML which included SNP-A karyotyping and mutational screen for IDH1/2, RAS, JAK2, UTX and EZH2 showed that various genes involved in epigenetic regulation may be especially affected by mutations in CMML.
Recurrent DNMT3A Mutations in Patients with Myelodysplastic Syndromes
TLDR
DNMT3A mutations were expressed in the majority of cells in all tested mutant samples regardless of myeloblast counts, suggesting that DNMT3B mutations occur early in the course of MDS, and may have prognostic value in de novo MDS.
Novel homo- and hemizygous mutations in EZH2 in myeloid malignancies
TLDR
It can be postulated that areas of somatic UPD may identify regions that harbor mutations in the regions affected by the copy number neutral loss of heterozygosity/UPD.
UTX Mutations and Epigenetic Changes In MDS/MPN and Related Myeloid Malignancies
TLDR
The results suggest that UTX gene may be involved in epigenetic regulation of promoters through site-specific histone demethylation function, thereby promoting repression of tumor suppressor genes.
TET2 mutation is an independent favorable prognostic factor in myelodysplastic syndromes (MDSs).
TLDR
Results indicate that TET2 mutations observed in approximately 20% of patients, irrespective of the World Health Organization or French-American-British subtype, represent a molecular marker for good prognosis in MDS.
GATA2 is a New Predisposition Gene for Familial Myelodysplastic Syndrome (MDS) and Acute Myeloid Leukemia (AML)
TLDR
It is indicated that the down regulation of proapoptotic BCL-xS by T354M, but not WT, may be responsible for this phenotype, and competition assays show that these mutations may be acting in a dominant negative fashion in some biological contexts.
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