Increased plasma d-2-hydroxyglutarate in isocitrate dehydrogenase 2-mutated blastic plasmacytoid dendritic cell neoplasm

Hum Pathol. 2015 Feb;46(2):322-6. doi: 10.1016/j.humpath.2014.10.013. Epub 2014 Nov 4.

Abstract

Blastic plasmacytoid dendritic cell neoplasm is an exceedingly rare hematologic malignancy derived from the precursors of plasmacytoid dendritic cells. Mutations in isocitrate dehydrogenase (IDH) 1 and 2 genes have been discovered in a range of neoplasms including glioma, acute myeloid leukemia, chondrosarcoma, and intrahepatic cholangiocarcinoma. Mutant IDH acquires neomorphic enzymatic activity to generate the oncometabolite d-2-hydroxyglutarate (d-2HG). Here, we describe the first case of an IDH2 R140Q-mutated blastic plasmacytoid dendritic cell neoplasm in a patient with markedly elevated plasma d-2HG. This finding expands the spectrum of neoplasms with increased d-2HG in association with IDH mutation. The roles of IDH mutation and d-2HG in disease pathogenesis and assessment of clinical response are discussed.

Keywords: Blastic plasmacytoid dendritic cell neoplasm; Hypermethylation; IDH mutation; Oncometabolite; d-2-hydroxyglutarate.

Publication types

  • Case Reports

MeSH terms

  • Aged
  • Dendritic Cells / metabolism*
  • Dendritic Cells / pathology*
  • Female
  • Glutarates / blood*
  • Hematologic Neoplasms / diagnosis*
  • Humans
  • Isocitrate Dehydrogenase / genetics*
  • Mutation / genetics*

Substances

  • Glutarates
  • alpha-hydroxyglutarate
  • Isocitrate Dehydrogenase