Bone Marrow Mast Cell Antibody-Targetable Cell Surface Protein Expression Profiles in Systemic Mastocytosis

Abstract

Despite recent therapeutic advances, systemic mastocytosis (SM) remains an incurable disease due to limited complete remission (CR) rates even after novel therapies. To date, no study has evaluated the expression on SM bone marrow mast cells (BMMC) of large panel of cell surface suitable for antibody-targeted therapy. In this study, we analyzed the expression profile of six cell-surface proteins for which antibody-based therapies are available, on BMMC from 166 SM patients vs. 40 controls. Overall, variable patterns of expression for the markers evaluated were observed among SM BMMC. Thus, CD22, CD30, and CD123, while expressed on BMMC from patients within every subtype of SM, showed highly variable patterns with a significant fraction of negative cases among advanced SM (aggressive SM (ASM), ASM with an associated clonal non-MC lineage disease (ASM-AHN) and MC leukemia (MCL)), 36%, 46%, and 39%, respectively. In turn, CD25 and FcεRI were found to be expressed in most cases (89% and 92%) in virtually all BMMC (median: 92% and 95%) from both indolent and advanced SM, but with lower/absent levels in a significant fraction of MC leukemia (MCL) and both in MCL and well-differentiated SM (WDSM) patients, respectively. In contrast, CD33 was the only marker expressed on all BMMC from every SM patient. Thus, CD33 emerges as the best potentially targetable cell-surface membrane marker in SM, particularly in advanced SM.

Establishing diagnostic criteria for mastocytosis in skin biopsies

“…[7][8][9][10][11][12] When involving the skin, neoplastic mast cells tend to have normal cytological features and do not differ from reactive mast cells; hence, we currently lack a specific marker for neoplastic mast cells in the skin, 13,14 in contrast with the well-known marker CD25 for neoplastic cells in the bone marrow. [15][16][17][18][19][20] Although several studies have shown that CD25 expression by mast cells in the skin was predictive of SM, [21][22][23] this immunostaining may not be applicable to CM. In fact, it has been shown that CD25 expression in the skin is not a reliable marker.…”

Mast Cells, Neuroinflammation and Pain in Fibromyalgia Syndrome

“…Finally, mast cells can release extracellular vesicles (exosomes) (Skokos et al, 2002, 2003) that could deliver regulatory molecules, including mtDNA and microRNAs (Kawikova and Askenase, 2014). Such microvesicles have been implicated in brain disorders (Tsilioni et al, 2014; Kawikova and Askenase, 2014) and pain disorders (Rafiee et al, 2018; Silva-Freire et al, 2019). We recently reported that extracellular vesicles are increased in the serum of children with ASD, contained mtDNA and stimulated cultured human microglia to secrete the pro-inflammatory molecules IL-1β and CXCL8 (Tsilioni and Theoharides, 2018).…”

KIT D816V Mast Cells Derived from Induced Pluripotent Stem Cells Recapitulate Systemic Mastocytosis Transcriptional Profile

“…CD2 expression was not detected on the surface of KIT D816V or control MC. CD33, a pan-myeloid marker also used as a criterion in SM disease diagnosis and a potential therapeutic cell surface target, was highly expressed in both, KIT D816V and control MCs ( Figure 2 F) [ 11 , 40 ].…”