Year: 2019
Type: review
Abstract: Our knowledge about the genetics of myelodysplastic syndromes (MDS) and related myeloid disorders has been dramatically improved during the past decade, in which revolutionized sequencing technologies have played a major role. Through intensive efforts of sequencing of a large number of MDS genomes, a comprehensive registry of driver mutations recurrently found in a recognizable fraction of MDS patients has been revealed, and ongoing efforts are being made to clarify their impacts on clinical phenotype and prognosis, as well as their role in the pathogenesis of MDS. Among major mutational targets in MDS are the molecules involved in DNA methylations, chromatin modification, RNA splicing, transcription, signal transduction, cohesin regulation, and DNA repair. Showing substantial overlaps with driver mutations seen in acute myeloid leukemia (AML), as well as age-related clonal hematopoiesis in healthy individuals, these mutations are presumed to have a common clonal origin. Mutations are thought to be acquired and positively selected in a well-organized manner to allow for expansion of the initiating clone to compromise normal hematopoiesis, ultimately giving rise to MDS and subsequent transformation to AML in many patients. Significant correlations between mutations suggest the presence of functional interactions between mutations, which dictate disease progression. Mutations are frequently associated with specific disease phenotype, drug response, and clinical outcomes, and thus, it is essential to be familiar with MDS genetics for better management of patients. This review aims to provide a brief overview of the recent progresses in MDS genetics.
Source: Blood
Author: Seishi Ogawa
Institutions: Kyoto University, Karolinska Institutet
Language: English
Subfield: Hematology
Field: Medicine
Domain: Health Sciences
Open Access status: bronze
Awards: G1923332730, G3959983577, 高齢者MDSにおけるクローン進化の経時的理解に基づく新たな治療戦略の構築, Investigation of the pathogeneisis of myelodysplastic syndromes and its therapeutic biomarkers, comprehensive studies on the molecular basis of early development and clonal evolution in cancer using advanced genomics., G7540847961
OpenAlex ID: W2913402023