Expression of Bcl-2 by human bone marrow mast cells and its overexpression in mast cell leukemia

Abstract

Bcl-2 protein plays a major role in the prevention of programmed cell death of differentiating cells. In the present study, the expression of cytoplasmic bcl-2 by human Bone Marrow Mast Cells (BMMC) from both normal and pathological bone marrow samples was examined. A total of 35 subjects corresponding to 9 healthy volunteers, 8 cases of adult indolent systemic mast cell disease (SMCD), 4 cases of pediatric mastocytosis (PM), 11 cases of hematological malignancies (HM), 2 cases of reactive bone marrow, and 1 case of mast cell leukemia (MCL) were analyzed. The expression of bcl-2 was studied using quantitative three-color flow cytometry. We also studied the molecular configuration of the bcl-2 gene and other relatives by Southern blot and polymerase chain reaction (PCR) in the MCL case. Bcl-2 expression was detected in BMMC from all samples analyzed. No significant differences on the expression of bcl-2 were detected between BMMC from healthy subjects and patients with SMCD, PM, HM, and reactive bone marrow. By contrast , bcl-2 protein was overexpressed in BMMC from MCL patient without gene rearrangement. Our results show that bcl-2 protein was constitutively expressed by BMMC. BMMC from MCL display overexpression of bcl-2, which could not be related to molecular rearrangements involving the bcl-2 gene. The expression of this protein by mature MC may play a role in the prevention of MC apoptosis and thus help to explain the long survival of these cells. The overexpression of bcl-2 by BMMC in MCL may help to explain their resistance to chemotherapy-induced apoptosis. Am.

Expression of Bcl-2 and Bcl-xL in Cutaneous and Bone Marrow Lesions of Mastocytosis

“…11,22 Two previous studies have addressed the role of bcl-2 proteins in mastocytosis. 34,35 Using immunohistochemistry, Jordan et al 34 have demonstrated that mast cells in focal bone marrow infiltrates of adult patients with systemic mastocytosis show strong immunoreactivity for bcl-xL, but usually fail to express bcl-2. Out of 22 patients investigated, only one patient with mast cell leukemia was found to express bcl-2 in a small fraction of bone marrow mast cells.…”

“…Out of 22 patients investigated, only one patient with mast cell leukemia was found to express bcl-2 in a small fraction of bone marrow mast cells. In accordance, Cervero et al 35 have reported on one patient with mast cell leukemia and overexpression of bcl-2, as assessed by quantitative flow cytometry, in bone marrow mast cells as well as peripheral blood mast cells that were present in this case. Eight other patients with indolent systemic mastocytosis expressed normal levels of bcl-2 in bone marrow mast cells.…”

“…Eight other patients with indolent systemic mastocytosis expressed normal levels of bcl-2 in bone marrow mast cells. 35 The present study shows, on the other hand, overexpression of bcl-2 and largely unaltered expression of bcl-xL in cutaneous mast cells in different forms of mastocytosis (Table 1; Figure 1, A and B; Figure 2). In addition, overexpression of bcl-xL compared to low or absent expression of bcl-2 in bone marrow lesions of patients with systemic mastocytosis was confirmed (Table 2; Figure 1, C and D).…”

“…34 In contrast, expression of bcl-2 was absent or low, with the exception of two patients with mast cell leukemia that exhibited higher levels of bcl-2 in their bone marrow. 34,35 In the present study, we show for the first time that bcl-2 expression is strongly enhanced in cutaneous mast cells of patients with different forms of mastocytosis, whereas expression of bcl-xL is mainly unaltered or only slightly increased in lesions of short duration. In the same patients, bone marrow infiltrates fail to express bcl-2, but strongly express bcl-xL.…”

Proapoptotic Bcl-2 family member Bim is involved in the control of mast cell survival and is induced together with Bcl-XL upon IgE-receptor activation

“…9,10 Knowledge about the role of Bcl-2 family members in the regulation of mast cell survival and apoptosis is limited. It has been shown that Bcl-2 and Bcl-X L are expressed in mast cells, [11][12][13] but very little is known about their function in these cells. It has been reported that baxÀ/À and bcl-2À/À mice have abnormal numbers of mast cells in certain tissues but no general difference with wt animals were observed.…”