The mutational landscape of paroxysmal nocturnal hemoglobinuria revealed: New insights into clonal dominance Comment uri icon

Overview

MeSH Major

  • Hemoglobinuria, Paroxysmal
  • High-Throughput Nucleotide Sequencing
  • Membrane Proteins

abstract

  • Paroxysmal nocturnal hemoglobinuria (PNH) is a disorder of hematopoietic stem cells that has largely been considered a monogenic disorder due to acquisition of mutations in the gene encoding PIGA, which is required for glycosylphosphatidylinositol (GPI) anchor biosynthesis. In this issue of the JCI, Shen et al. discovered that PNH is in fact a complex genetic disorder orchestrated by many genetic alterations in addition to PIGA mutations. Some of these mutations predate the acquisition of PIGA mutations, while others occur later. Surprisingly, this work indicates that PNH has a clonal evolution and architecture strikingly similar to that of other myeloid neoplasms, highlighting a potentially broader mechanism of disease pathogenesis in this disorder.

publication date

  • January 2014

Research

keywords

  • Comment

Identity

Digital Object Identifier (DOI)

  • 10.1172/JCI77984

PubMed ID

  • 25244089

Additional Document Info

start page

  • 4227

end page

  • 30

volume

  • 124

number

  • 10