Publication details

Plasma cells in patients with monoclonal gammopathies express neural stem cell marker nestin

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Year of publication 2010
Type Conference abstract
MU Faculty or unit

Faculty of Medicine

Description Introduction and aims: Nestin, an intermediate filament protein is known to be a characteristic marker of multipotent precursor cells with proliferation, migration and differentiation potential. During terminal differentiation nestin expression is downregulated but can be reactivated after injury or other pathological conditions. Nestin is also detected in many solid tumors where it plays a role in an aggressive behavior, migration and proliferation of cells and seems to be a reliable diagnostics and predictive indicator of malignancy. The aim of this pilot study was confirmed nestin expression in malignant plasma cells (PC) in patients with monoclonal gammopathy (MG). Methods: A total number of 34 MG patients (21M/13F; median age 68 years) represented by 91% (31/34) of MM patients, 3% (1/34) of MGUS patients, 3% (1/34) of non-secretory MM patients and 3% (1/34) of plasma cell leukemia (PCL) patients were included in this pilot study. Five patients without monoclonal gammopathy served as a control group. Bone marrow mononuclear cells were analysed by 3-color flow cytometry, and PCs were identified as CD38+CD138+ followed by direct staining for intracellular nestin. Nestin expression was assessed based on percentage of PCs showing positivity for nestin (Nes+PC) and median fluorescence intensity (MFI) of nestin expression in PCs. Nestin expression was verified in 3 representative samples by indirect immunofluorescence and in 7 representative samples by western blots. Results: Flow cytometric analysis confirmed heterogeneous expression of nestin among 34 MG patients. The whole group of MG patients had the median percentage of Nes+PC 21,2% (range, 0%-95.4%). In the control group, the median percentage of Nes+ PC did not exceed 0.3% (range, 0%-2.7%). MFI of nestin expression in PC was 442 (range, 0-6764). Indirect immunofluorescence demonstrated nestin immunoreactivity in all 3 analyzed samples as the network of nestin filaments or the diffused signal in the cytoplasm of PC. Western blot analyses confirmed nestin expression in all 7 MM cases. Conclusion: In our pilot study we confirmed as first nestin expression on protein level in CD138+CD38+ PC of 34 MG patients and quantified by flow cytometry. Nestin expression in malignant PC, that are thought to be quiescence and terminally differentiated, is entirely new phenomenon. It requires our attention and further study to elucidate the role of this protein in pathogenesis of monoclonal gammopathies. Supported with research program: VC MŠMT ČR LC06027 and P304/10/1395.
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