title: CD123 immunostaining patterns in systemic mastocytosis: differential expression in disease subgroups and potential prognostic value.
abstract: CD123 is the α-subunit of the interleukin-3 receptor; it represents a potential therapeutic target in systemic mastocytosis (SM) given its absent expression on normal/reactive mast cells (MCs) and aberrant expression on neoplastic MCs. We studied 58 SM patients to define CD123 expression patterns by immunohistochemistry and its clinical significance. Two hematopathologists independently scored bone marrow slides using predefined histologic parameters. In all, 23 patients had indolent SM (ISM), 10 aggressive SM (ASM), 23 SM with associated hematological neoplasm (SM-AHN) and 2 had mast cell leukemia (MCL). MC_CD123 expression was demonstrable in 37 (64%) cases; expression rates were 100%, 61%, 57% and 0% in ASM, ISM, SM-AHN and MCL, respectively (P=0.02). Focal proliferation of plasmacytoid dendritic cells (PDCs) around MC aggregates, suggesting a tumor-promoting role for PDCs, was noted in 44 (76%) cases, and was significantly higher in CD123-positive versus -negative cases (87% versus 50%, P=0.005). CD123 expression and its staining intensity had prognostic value in SM-chronic myelomonocytic leukemia and nonindolent SM patients, respectively. These observations suggest that targeting CD123 in SM may have direct (via MCs) and indirect (via PDCs) antitumor effects and clinical trials to that effect require laboratory correlative studies to address the observed target expression heterogeneity.
authors.affiliation: Division of Hematology, Department of Internal Medicine, Mayo Clinic, Rochester, MN, USA.
authors.forename: A
authors.initials: A
authors.lastname: Pardanani
authors.affiliation: Division of Hematopathology, Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, MN, USA.
authors.forename: K K
authors.initials: KK
authors.lastname: Reichard
authors.affiliation: Division of Hematology, Department of Internal Medicine, Mayo Clinic, Rochester, MN, USA.
authors.forename: D
authors.initials: D
authors.lastname: Zblewski
authors.affiliation: Division of Hematology, Department of Internal Medicine, Mayo Clinic, Rochester, MN, USA.
authors.forename: R A
authors.initials: RA
authors.lastname: Abdelrahman
authors.affiliation: Division of Hematology, Department of Internal Medicine, Mayo Clinic, Rochester, MN, USA.
authors.forename: E A
authors.initials: EA
authors.lastname: Wassie
authors.affiliation: Division of Hematopathology, Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, MN, USA.
authors.forename: W G
authors.initials: WG
authors.lastname: Morice Ii
authors.affiliation: Stemline Therapeutics Inc., New York, NY, USA.
authors.forename: C
authors.initials: C
authors.lastname: Brooks
authors.affiliation: Division of Hematopathology, Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, MN, USA.
authors.forename: K L
authors.initials: KL
authors.lastname: Grogg
authors.affiliation: Division of Hematopathology, Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, MN, USA.
authors.forename: C A
authors.initials: CA
authors.lastname: Hanson
authors.affiliation: Division of Hematology, Department of Internal Medicine, Mayo Clinic, Rochester, MN, USA.
authors.forename: A
authors.initials: A
authors.lastname: Tefferi
authors.affiliation: Division of Hematopathology, Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, MN, USA.
authors.forename: D
authors.initials: D
authors.lastname: Chen
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000378:metabolism*; D005260:Female; D005500:Follow-Up Studies; D019337:Hematologic Neoplasms / Q000378:metabolism* / Q000473:pathology; D006801:Humans; D007124:Immunoenzyme Techniques; D053650:Interleukin-3 Receptor alpha Subunit / Q000378:metabolism*; D007946:Leukemia, Mast-Cell / Q000378:metabolism* / Q000473:pathology; D008297:Male; D034721:Mastocytosis, Systemic / Q000378:metabolism* / Q000473:pathology; D008875:Middle Aged; D009367:Neoplasm Staging; D011379:Prognosis; D012189:Retrospective Studies
chemical_list: D014408:Biomarkers, Tumor; C115022:IL3RA protein, human; D053650:Interleukin-3 Receptor alpha Subunit