MDS: Recent progress in molecular pathogenesis and clinical aspects

DOI Web Site PubMed
  • HARADA Hironori
    Laboratory of Oncology, Department of Medical Science, Tokyo University of Pharmacy and Life Sciences

Bibliographic Information

Other Title
  • MDS分子病態研究の進歩
  • MDS ブンシ ビョウタイ ケンキュウ ノ シンポ

Search this article

Abstract

<p>Myelodysplastic syndromes (MDS) are defined as hematopoietic stem cell disorders caused by various gene abnormalities. Recent analysis using next generation sequencing has provided great progress in identifying relationships between gene mutations and clinical phenotypes of MDS. It is estimated that one or more gene mutations occur in greater than 90% of MDS patients. More than 50 gene mutations affecting RNA splicing machinery, DNA methylation, histone modifications, transcription factors, signal transduction proteins, and components of the cohesion complex participate in the pathogenesis of MDS. The sequential accumulation of additional cooperating mutations drives disease evolution from clonal hematopoiesis of indeterminate potential (CHIP) to symptomatic MDS and from MDS to acute myelogenous leukemia (AML). Mutations in RNA splicing and DNA methylation occur early and are considered founding mutations, whereas others that occur later are regarded as subclonal mutations. RUNX1 mutations are more likely to be subclonal; however, they apparently play a pivotal role in familial MDS. In addition, large alterations of chromosomes are involved in the pathogenesis of MDS. 5q− syndrome, which leads to haploinsufficiency of the located genes, has consistent clinical features. Understanding gene abnormalities of MDS patients can provide clinical information, including diagnosis, prognostic score, and prediction of response to therapy.</p>

Journal

  • Rinsho Ketsueki

    Rinsho Ketsueki 58 (10), 1941-1950, 2017

    The Japanese Society of Hematology

Related Projects

See more

Keywords

Details 詳細情報について

Report a problem

Back to top