Immunophenotype of Bone Marrow Mast Cells in Indolent Systemic Mast Cell Disease in Adults

Abstract

One of the major advances in the histological diagnosis of bone marrow (BM) involvement in mastocytosis has been the specific immunohistochemical detection of tryptase on most cells (MC), which has shown to be of great diagnostic value, especially in cases of malignant mastocytosis. On the other hand, recent studies have clearly shown that bone marrow mast cells can be specifically identified and accurately enumerated using multiparametric flow cytometry, which allow a systematic analysis of the immunophenotypic characteristics of bone marrow mast cells. Once this flow cytometric approach was applied for the analysis of BMMC from mastocytosis patients clear immunophenotypical differences were found between BMMC from normal individuals and adults with mastocytosis. The most characteristic immunophenotypic feature, both in malignant and adult indolent systemic mast cell disease, being the coexpression of CD2 and CD25 antigens, never present in normal bone marrow mast cells and, which constitute an aberrant hallmark of bone marrow mast cells in adult mastocytosis. Furthermore, bone mast cells from mastocytosis display a higher reactivity for CD35, CD63, and CD69 activation-associated antigens. Based on these results it could be concluded that the use of multiparametric flow cytometric immunophenotyping of BMMC in adult patients suffering from cutaneous mastocytosis can be of great utility for the diagnosis of BM involvement; additionally, this might also help to establish the real incidence of BM involvement in cutaneous mastocytosis.

Repressible transgenic model of NRAS oncogene–driven mast cell disease in the mouse

“…[73][74][75][76] The surrogate hCD2 marker introduced with the NRASV12 transgene may contribute to the development of the ASM phenotype described here. Although the intracellular portion of CD2 has been deleted, the extracellular domain may engage antigen-presenting cells in the mouse.…”

Immunophenotypic Characterization of Bone Marrow Mast Cells in Mastocytosis and Other Mast Cell Disorders

“…(Source: Bodni et al, 2003;Diaz-Agustin et al, 1999;Escribano et al, 1995Escribano et al, , 1997Escribano et al, , 1998bEscribano et al, , 1998cEscribano et al, , 1998dEscribano et al, , 1999Escribano et al, , 2001Escribano et al, , 2002Escribano et al, , 2006Nun˜ez et al, 2002;Orfao et al, 1996;Pardanani et al, 2004;Teodosio et al, 2010;Valent et al, 2001b. (Source: Bodni et al, 2003;Diaz-Agustin et al, 1999;Escribano et al, 1995Escribano et al, , 1997Escribano et al, , 1998bEscribano et al, , 1998cEscribano et al, , 1998dEscribano et al, , 1999Escribano et al, , 2001Escribano et al, , 2002Escribano et al, , 2006Nun˜ez et al, 2002;Orfao et al, 1996;Pardanani et al, 2004;Teodosio et al, 2010;Valent et al, 2001b.…”

Abnormal Expression of CD Antigens in Mastocytosis

“…Apart from the aberrant expression of CD2 and CD25, quantitative FCM studies of BMMC from indolent systemic mastocytosis (ISM) [10], aggressive systemic mastocytosis, and isolated BM mastocytosis [Escribano et al, unpubl. data] have shown that, similarly, BMMC from these conditions also show a lower expression of the CD117 antigen and abnormally high levels of expression of the CD29 and CD33 antigens [11, 12, 13]. Interestingly, three activation-associated antigens (CD35, CD63 [14], and CD69 [15]) have been reported as overexpressed in MC from mastocytosis as well.…”

“…Interestingly, three activation-associated antigens (CD35, CD63 [14], and CD69 [15]) have been reported as overexpressed in MC from mastocytosis as well. Overall, these unique phenotypic features are of great relevance for the differential diagnosis of BM involvement in patients with mastocytosis, since almost no overlap was found between the levels of expression on BMMC from ISM and aggressive systemic mastocytosis patients and those found in other groups of individuals [revised in 11, 12, 13]. Additional phenotypic differences between normal BMMC and BMMC from mastocytosis patients include overexpression of complement-related antigens such as CD11c, CD58 [Núñez et al, unpubl.…”