Molecular Pathogenesis and Treatment of Myelodysplastic Syndromes

Myelodysplastic syndromes (MDS) are clonal hematological disorders arising from hematopoietic stem cells that have accumulated various genetic abnormalities. MDS are heterogeneous in nature but uniformly characterized by chronic and progressive cytopenia from ineffective hematopoiesis, dysplasia in...

Full description

Saved in:
Bibliographic Details
Published in:Internal Medicine 2021/01/01, Vol.60(1), pp.15-23
Main Author: Nakajima, Hideaki
Format: Article
Language:English
Subjects:
Cohesin
Deoxyribonucleic acid
DNA
DNA Methylation
DNA repair
Dysplasia
epigenome
Evolutionary genetics
Genetic transformation
genome
Hematological diseases
Hematopoietic stem cells
Histones
Humans
Internal medicine
Leukemia, Myeloid, Acute - genetics
MDS
molecular pathogenesis
Mutation
Myelodysplastic syndrome
myelodysplastic syndromes
Myelodysplastic Syndromes - genetics
Myelodysplastic Syndromes - therapy
Next-generation sequencing
Pathogenesis
Review
Ribonucleic acid
RNA
RNA Splicing
Signal transduction
Stem cells
treatment
Citations: Items that this one cites
Items that cite this one
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary:Myelodysplastic syndromes (MDS) are clonal hematological disorders arising from hematopoietic stem cells that have accumulated various genetic abnormalities. MDS are heterogeneous in nature but uniformly characterized by chronic and progressive cytopenia from ineffective hematopoiesis, dysplasia in single or multiple lineages, and transformation to acute leukemia in a subset of patients. The genomic landscape revealed by next-generation sequencing has provided a comprehensive picture of the molecular pathways involved in MDS pathogenesis. Recurrent mutational targets in MDS are the genes involved in RNA splicing, DNA methylation, histone modification, transcription, signal transduction, cohesin complex and DNA repair. Sequential acquisition of mutations in these sets of genes serves as a driver for the initiation, clonal evolution and progression of MDS. Based on these findings, novel agents targeting driver mutations of MDS are currently under development and expected to improve the clinical outcome of MDS in the coming decades.
ISSN:0918-2918
1349-7235
DOI:10.2169/internalmedicine.4214-19