Increased Mast Cell Numbers in Bone Marrow of Patients with Myeloproliferative Neoplasms and Pruritus.
Key claim: Untreated MPN patients with clinically significant pruritus have significantly higher absolute and relative bone-marrow mast-cell numbers than those without pruritus.
Abstract
Pruritus may be a debilitating symptom in cases of myeloproliferative neoplasm (MPN). Since mast cells (MCs) play a pivotal role, we hypothesized that bone marrow (BM) MCs contribute to the occurrence of pruritus. In this exploratory study, untreated MPN patients were included. BM aspirate/biopsy/blood samples and responses to the MPN-Symptom Assessment Form were obtained. Thirty-two patients were included (essential thrombocythemia, n=19; polycythemia vera, n=7; primary myelofibrosis, n=6). Eleven had clinically significant pruritus (35%). The absolute MC count and proportion per total nucleated BM cells were significantly higher in patients with pruritus compared to those without (mean of 25.5 vs. 58.1 MCs/mm, p=0.032 and 0.59% vs. 1.66%, p=0.041, respectively). MC immunophenotypes and serum levels of tryptase, interleukin-6, tumor necrosis factor alpha, and soluble CD117 were not correlated. Thus, this study showed that absolute and relative MC numbers are increased in cases of MPN with pruritus. However, whether MCs play a pathophysiological role in causing pruritus or are bystanders remains to be determined.
Why this matters
Pruritus in MPN is often refractory and mechanistically ascribed to mast cells and leukotrienes, but direct clinical quantification has been limited. Documenting elevated bone-marrow mast-cell counts in symptomatic patients strengthens the rationale for mast-cell- and mediator-directed therapies (antihistamines, leukotriene antagonists, mast-cell stabilizers) as symptom-management options and suggests bone-marrow mast-cell density could become a correlative biomarker for pruritus severity studies.