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.

International prognostic scoring system for mastocytosis (IPSM): a retrospective cohort study

“…During the past two decades, several clinical, serological, cytomorphological, immunological, and molecular variables have been reported to be of prognostic significance in mastocytosis. [10][11][12][13][14][15][16][17][18][19] Several of these variables have been included in the WHO classification, such as organomegaly or cytopenias. 2,3 Other adverse prognostic variables include absence of skin lesions, multilineage involvement with KIT Asp816Val, mutations in genes other than KIT (eg, SRSF2, ASXL1, or RUNX1), increased amounts of β 2microglobulin in serum, and raised amounts of alkaline phosphatase.…”

“…2,3 Other adverse prognostic variables include absence of skin lesions, multilineage involvement with KIT Asp816Val, mutations in genes other than KIT (eg, SRSF2, ASXL1, or RUNX1), increased amounts of β 2microglobulin in serum, and raised amounts of alkaline phosphatase. 10,[12][13][14][15][16][17][18][19] However, these variables were studied in smaller patients' cohorts and without comparing all potential risk factors with each other in multivariate analyses. Moreover, several of these variables (eg, molecular profiling) are not available at all centres.…”

The clinical and pathological panoply of systemic mastocytosis

“…Chronic MCL is defined by mature mast cell morphology and an indolent course.Mast cells in MCL tend to be immature and lose the spindle shape conventionally seen in ISM.Morphologic variants include a spectrum from blast‐like, round to spindle‐shaped cells with varying degrees of granularity. Some forms may have coarse purple granules (Georgin‐Lavialle et al, ; Valent et al, ; Swerdlow et al, ).Patients with MCL have the poorest overall survival (Pardanani et al, ) and should be considered for trials using newer targeted agents, high dose chemotherapy and bone marrow transplant if clinically eligible.…”

“…CD2 expression on mast cells is more frequently seen when using flow cytometry. Expression of CD30 and/or CD123 may help in identifying patients who may progress in the future, but data on this association is not particularly robust Valent et al, 2011;Moonim et al, 2012;Morgado et al, 2013;Doyle et al, 2014;Blatt et al, 2015;Pardanani et al, 2016).…”

Targeted Treatment Options in Mastocytosis

“…CD123, the α-subunit of the interleukin-3 receptor, represents also a potential therapeutic target as it is aberrantly expressed on neoplastic MCs and absent on normal MCs (82, 83). Clinical trials are ongoing to evaluate its efficacy in patients with SM.…”