Mechanisms of allergy and clinical immunologyMast cells from different molecular and prognostic subtypes of systemic mastocytosis display distinct immunophenotypes
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Patients, controls, and samples
A total of 215 BM samples were obtained from adult individuals, including 123 patients (66 men and 57 women; median age, 45 years; range, 19-83 years) consecutively diagnosed with SM27 at the reference centers of the Spanish Network on Mastocytosis (REMA; Mast Cell Unit, Hospital Virgen del Valle, Toledo; and Cytometry Service, Cancer Research Centre, Salamanca, Spain)1,8 and 92 normal BM donors, which included 40 normal subjects and 52 patients undergoing BM aspiration for clinical reasons
Flow-cytometric pattern of BM infiltration by MCs
Patients with SM displayed increased BMMC counts (mean ± 1 SD) versus normal BM (1.7% ± 6.8% vs 0.07% ± 0.11%; P < .0001). ASM, MCL, and SM-AHNMD showed significantly higher BMMC counts than cMCAD and ISM (P < .05; Table E1).
Immunophenotypic characteristics of normal/reactive BMMCs
Normal/reactive (control) BMMCs displayed relatively high light scatter values and expressed the CD45, CD117, CD63, CD203c, CD59, FcεRI, CD32, HLA-I, cytoplasmic carboxypeptidase, and cytoplasmic total tryptase (CyB12; Fig 1, Fig 2, Fig 3) markers in the absence of
Discussion
Systemic mastocytosis is a clinically and prognostically heterogeneous group of disorders1, 8, 16, 17, 18, 19 characterized by the clonal expansion of immunophenotypically aberrant MCs in the patients' BM.6, 7, 9, 10, 11 However, little is known about the specific immunophenotypic features of the distinct variants of SM. Here, we analyzed the expression of a broad panel of functional proteins on BMMCs from a large cohort of patients with SM compared with normal/reactive BMMCs. Overall, aberrant
References (42)
- et al.
Diagnostic criteria and classification of mastocytosis: a consensus proposal
Leuk Res
(2001) - et al.
Morphologic properties of neoplastic mast cells: delineation of stages of maturation and implication for cytological grading of mastocytosis
Leuk Res
(2001) - et al.
Expression, epitope analysis, and functional role of the LFA-2 antigen detectable on neoplastic mast cells
Blood
(2001) - et al.
Flow cytometric analysis of normal and neoplastic mast cells: role in diagnosis and follow-up of mast cell disease
Immunol Allergy Clin North Am
(2006) - et al.
Indolent systemic mast cell disease in adults: immunophenotypic characterization of bone marrow mast cells and its diagnostic implications
Blood
(1998) - et al.
KIT mutation in mast cells and other bone marrow hematopoietic cell lineages in systemic mast cell disorders: a prospective study of the Spanish Network on Mastocytosis (REMA) in a series of 113 patients
Blood
(2006) - et al.
A novel form of mastocytosis associated with a transmembrane c-kit mutation and response to imatinib
Blood
(2004) - et al.
Well-differentiated systemic mastocytosis: a new disease variant with mature mast cell phenotype and lack of codon 816 c-Kit mutations
J Allergy Clin Immunol
(2004) - et al.
Clonal mast cell disorders in patients with systemic reactions to Hymenoptera stings and increased serum tryptase levels
J Allergy Clin Immunol
(2009) - et al.
Demonstration of an aberrant mast-cell population with clonal markers in a subset of patients with “idiopathic” anaphylaxis
Blood
(2007)
Bone marrow mast cell immunophenotyping in adults with mast cell disease: a prospective study of 33 patients
Leuk Res
Prognosis in adult indolent systemic mastocytosis: a long-term study of the Spanish Network on Mastocytosis in a series of 145 patients
J Allergy Clin Immunol
One-step detection of c-kit point mutations using peptide nucleic acid-mediated polymerase chain reaction clamping and hybridization probes
Am J Pathol
Utility of flow cytometric analysis of mast cells in the diagnosis and classification of adult mastocytosis
Leuk Res
Mast cells in allergy: innate instructors of adaptive responses
Immunobiology
Expression of Bcl-2 and Bcl-xL in cutaneous and bone marrow lesions of mastocytosis
Am J Pathol
Mast cells cultured from the peripheral blood of normal donors and patients with mastocytosis originate from a CD34+/Fc epsilon RI- cell population
Blood
Bone marrow mast cell morphologic features and hematopoietic dyspoiesis in systemic mast cell disease
Hematopathology
Evaluation of neoplastic human mast cells by tryptase-immunoelectron microscopy
Histopathology
Mastocytosis (mast cell disease). In: Jaffe ES, Harris NL, Stein H, Vardiman JW, eds. World Health Organization (WHO) classification of tumours. Pathology and genetics of tumours of haematopoietic and lymphoid tissues
Human bone marrow mast cells from indolent systemic mast cell disease constitutively express increased amounts of the CD63 protein on their surface
Cytometry
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Supported by grants from the Fondo de Investigaciones Sanitarias of the Ministerio de Sanidad y Consumo of Spain (REMA G03/007, PI050726, PI061377, PI060529, and RETICS RD06/0020/0035-FEDER); Junta de Castilla y León (Grant SAN/1778/2009); Junta de Comunidades de Castilla La Mancha (FISCAM 2007/36), and Fundación MMA. A.C.G.-M. is supported by a grant from Fondo de Investigaciones Sanitarias/FEDER (CP03/00035). C.T. is supported by a grant from the Fundação para a Ciência e Tecnologia of Portugal (SFRH/BD/17545/2004). L.B.S. is supported by grants from the National Institutes of Health (AI27517 and AI077435).
Disclosure of potential conflict of interest: L. B. Schwartz is on the speakers' bureau and is a consultant for Novartis/Genentech; is the inventor of the tryptase assay for Phadia; receives grant support from the NIH, GlaxoSmithKline, Novartis/Genentech, Pharming, and Ception; has provided legal consultation or expert witness testimony in cases related to anaphylaxis; is on the Board of Directors for AAFA and CIS; and is on the Program Directors' Board for the AAAAI. The rest of the authors have declared that they have no conflict of interest.
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These authors contributed equally to this work.
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These authors contributed equally to this work.