CD123 Immunostaining Patterns in Systemic Mastocytosis
CD123 is the α-subunit of the high-affinity receptor for interleukin-3. CD123 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.
Mayo Clinic researchers (first author Animesh Pardanani, M.B.B.S., Ph.D.) studied 58 SM patients to define CD123 expression patterns by immunohistochemistry and its clinical significance. The study, published in the journal Leukemia, was conducted to determine:
- Whether there is a significant difference in CD123 expression between SM subtypes
- Whether focal plasmacytoid dendritic cells (PDCs) proliferation around MC aggregates is correlated with CD123 expression
- Whether CD123 expression has prognostic value for overall survival
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 cases. Focal proliferation of PDCs around MC aggregates, suggesting a tumor-promoting role for PDCs, was noted in 44 cases, and was significantly higher in CD123-positive versus negative cases. CD123 expression and its staining intensity had prognostic value in SM-chronic myelomonocytic leukemia and nonindolent SM patients, respectively.
These results 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.