TY - JOUR
T1 - CD123 immunostaining patterns in systemic mastocytosis
T2 - Differential expression in disease subgroups and potential prognostic value
AU - Pardanani, A.
AU - Reichard, K. K.
AU - Zblewski, D.
AU - Abdelrahman, R. A.
AU - Wassie, E. A.
AU - Morice, W. G.
AU - Brooks, C.
AU - Grogg, K. L.
AU - Hanson, C. A.
AU - Tefferi, A.
AU - Chen, D.
N1 - Publisher Copyright:
© 2016 Macmillan Publishers Limited.
PY - 2016/4/1
Y1 - 2016/4/1
N2 - 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.
AB - 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.
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U2 - 10.1038/leu.2015.348
DO - 10.1038/leu.2015.348
M3 - Article
C2 - 26678095
AN - SCOPUS:84954537892
SN - 0887-6924
VL - 30
SP - 914
EP - 918
JO - Leukemia
JF - Leukemia
IS - 4
ER -