Mast cells from different molecular and prognostic subtypes of systemic mastocytosis display distinct immunophenotypes

Background

Systemic mastocytosis (SM) is a heterogeneous group of disorders with distinct clinical and biological behavior. Despite this, little is known about the immunophenotypic features of the distinct diagnostic categories of SM.

Objective

To analyze the immunophenotypic characteristics of bone marrow (BM) mast cells (MCs) of different subtypes of SM.

Methods

Bone marrow samples from 123 patients with different subtypes of SM and 92 controls were analyzed for a broad panel of immunophenotypic markers by flow cytometry.

Results

Three clearly different maturation-associated immunophenotypic profiles were found for BMMCs in SM. These different profiles were associated with both genetic markers of the disease and its clinical behavior. BMMCs from poor-prognosis categories of SM (aggressive SM and MC leukemia) typically showed an immature phenotype with clonal involvement of all myeloid lineages by the D816V stem cell growth factor receptor gene (KIT) mutation. In turn, a mature activated versus resting BMMC immunophenotype was commonly found among patients with good-prognosis subtypes of SM depending on whether they carried (indolent SM and clonal MC activation disorders) or not (well differentiated SM) the D816V KIT mutation.

Conclusion

Bone marrow MCs from SM show 3 different maturation-related immunophenotypic profiles that are associated with both the genetic markers of the disease and its clinical behavior.

Key words: Mastocytosis, immunophenotype, flow cytometry, KIT mutations

Abbreviations used: ASM, Aggressive systemic mastocytosis, ASM-AHNMD, Aggressive systemic mastocytosis associated with a clonal non–mast cell lineage hematopoietic disease, BM, Bone marrow, cMCAD, Clonal mast cell activation disorder, CPA, Carboxypeptidase A, CyB12, Cytoplasmic total tryptase, CyG5, Cytoplasmic mature tryptase, FDR, False discovery rate, ISM, Indolent systemic mastocytosis, ISM-AHNMD, Indolent systemic mastocytosis associated with a clonal non–mast cell lineage hematopoietic disease, MC, Mast cell, MCL, Mast cell leukemia, NPV, Negative predictive value, PPV, Positive predictive value, SM, Systemic mastocytosis, SM-AHNMD, Systemic mastocytosis associated with a clonal non–mast cell lineage hematopoietic disease, SSC, Sideward light scatter, sT, Serum tryptase, TN, True negative, TP, True positive, WDSM, Well differentiated systemic mastocytosis