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... Show moreDespite 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 Fc epsilon RI 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. Show less
Mayado, A.; Teodosio, C.; Dasilva-Freire, N.; Jara-Acevedo, M.; Garcia-Montero, A.C.; Alvarez-Twose, I.; ... ; Orfao, A. 2018
BackgroundRecent studies show that most systemic mastocytosis (SM) patients, including indolent SM (ISM) with (ISMs+) and without skin lesions (ISMs-), carry the KIT D816V mutation in PB leukocytes... Show moreBackgroundRecent studies show that most systemic mastocytosis (SM) patients, including indolent SM (ISM) with (ISMs+) and without skin lesions (ISMs-), carry the KIT D816V mutation in PB leukocytes. We investigated the potential association between the degree of involvement of BM hematopoiesis by the KIT D816V mutation and the distribution of different maturation-associated compartments of bone marrow (BM) and peripheral blood (PB) CD34(+) hematopoietic precursors (HPC) in ISM and identified the specific PB cell compartments that carry this mutation.MethodsThe distribution of different maturation-associated subsets of BM and PB CD34(+) HPC from 64 newly diagnosed (KIT-mutated) ISM patients and 14 healthy controls was analyzed by flow cytometry. In 18 patients, distinct FACS-purified PB cell compartments were also investigated for the KIT mutation.ResultsISM patients showed higher percentages of both BM and PB MC-committed CD34(+) HPC vs controls, particularly among ISM cases with MC-restricted KIT mutation (ISMMC); this was associated with progressive blockade of maturation of CD34(+) HPC to the neutrophil lineage from ISMMC to multilineage KIT-mutated cases (ISMML). Regarding the frequency of KIT-mutated cases and cell populations in PB, variable patterns were observed, the percentage of KIT-mutated PB CD34(+) HPC, eosinophils, neutrophils, monocytes and T cells increasing from ISMs-(MC) and ISMs+(MC) to ISMML patients.ConclusionThe presence of the KIT D816V mutation in PB of ISM patients is associated with (early) involvement of circulating CD34(+) HPC and multiple myeloid cell subpopulations, KIT-mutated PB CD34(+) HPC potentially contributing to early dissemination of the disease. Show less
