CD123 immunostaining patterns in systemic mastocytosis: differential expression in disease subgroups and potential prognostic value

Animesh D Pardanani, K. K. Reichard, D. Zblewski, R. A. Abdelrahman, E. A. Wassie, W. G. Morice, C. Brooks, K. L. Grogg, C. A. Hanson, Ayalew Tefferi, D. Chen

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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.Leukemia advance online publication, 12 January 2016; doi:10.1038/leu.2015.348.

Original languageEnglish (US)
JournalLeukemia
DOIs
StateAccepted/In press - Dec 18 2015

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Systemic Mastocytosis
Mast Cells
Mast-Cell Leukemia
Dendritic Cells
Interleukin-3 Receptors
Leukemia, Myelomonocytic, Chronic
Hematologic Neoplasms
Publications
Leukemia
Bone Marrow
Immunohistochemistry
Clinical Trials
Staining and Labeling

ASJC Scopus subject areas

  • Hematology
  • Cancer Research
  • Anesthesiology and Pain Medicine

Cite this

CD123 immunostaining patterns in systemic mastocytosis : differential expression in disease subgroups and potential prognostic value. / Pardanani, Animesh D; Reichard, K. K.; Zblewski, D.; Abdelrahman, R. A.; Wassie, E. A.; Morice, W. G.; Brooks, C.; Grogg, K. L.; Hanson, C. A.; Tefferi, Ayalew; Chen, D.

In: Leukemia, 18.12.2015.

Research output: Contribution to journalArticle

Pardanani, Animesh D ; Reichard, K. K. ; Zblewski, D. ; Abdelrahman, R. A. ; Wassie, E. A. ; Morice, W. G. ; Brooks, C. ; Grogg, K. L. ; Hanson, C. A. ; Tefferi, Ayalew ; Chen, D. / CD123 immunostaining patterns in systemic mastocytosis : differential expression in disease subgroups and potential prognostic value. In: Leukemia. 2015.
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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.Leukemia advance online publication, 12 January 2016; doi:10.1038/leu.2015.348.",
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AU - Abdelrahman, R. A.

AU - Wassie, E. A.

AU - Morice, W. G.

AU - Brooks, C.

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