title: Increased plasma d-2-hydroxyglutarate in isocitrate dehydrogenase 2-mutated blastic plasmacytoid dendritic cell neoplasm.
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.
authors.affiliation: Department of Pathology, University of Texas Southwestern Medical Center, Dallas, TX 75390; Department of Pediatrics, University of Texas Southwestern Medical Center, Dallas, TX 75390; Division of Pathology and Laboratory Medicine, Children's Medical Center, Dallas, TX 75235.
authors.forename: Dinesh
authors.initials: D
authors.lastname: Rakheja
authors.affiliation: Department of Pathology, University of Texas Southwestern Medical Center, Dallas, TX 75390.
authors.forename: Franklin
authors.initials: F
authors.lastname: Fuda
authors.affiliation: Department of Pathology, University of Texas Southwestern Medical Center, Dallas, TX 75390; Department of Dermatology, University of Texas Southwestern Medical Center, Dallas, TX 75390.
authors.forename: Travis
authors.initials: T
authors.lastname: Vandergriff
authors.affiliation: Division of Pathology and Laboratory Medicine, Children's Medical Center, Dallas, TX 75235.
authors.forename: Richard
authors.initials: R
authors.lastname: Boriack
authors.affiliation: Department of Medicine, Division of Hematology, Stanford University School of Medicine, Stanford, CA.
authors.forename: Bruno C
authors.initials: BC
authors.lastname: Medeiros
authors.affiliation: Department of Internal Medicine, Division of Hematology/Oncology, University of Texas Southwestern Medical Center, Dallas, TX 75390.
authors.forename: Arthur E
authors.initials: AE
authors.lastname: Frankel
authors.affiliation: Department of Pathology, University of Texas Southwestern Medical Center, Dallas, TX 75390. Electronic address: weina.chen@utsouthwestern.edu.
authors.forename: Weina
authors.initials: W
authors.lastname: Chen
mesh_terms: D000368:Aged; D003713:Dendritic Cells / Q000378:metabolism* / Q000473:pathology*; D005260:Female; D005977:Glutarates / Q000097:blood*; D019337:Hematologic Neoplasms / Q000175:diagnosis*; D006801:Humans; D007521:Isocitrate Dehydrogenase / Q000235:genetics*; D009154:Mutation / Q000235:genetics*
chemical_list: D005977:Glutarates; C019417:alpha-hydroxyglutarate; D007521:Isocitrate Dehydrogenase
keywords: Blastic plasmacytoid dendritic cell neoplasm; Hypermethylation; IDH mutation; Oncometabolite; d-2-hydroxyglutarate