Cell cycle regulators in multiple myeloma: Prognostic implications of p53 nuclear accumulation

Pruneri, Giancarlo; Carboni, Nadia; Baldini, Luca; Intini, Daniela; Colombi, M.; Valentini, Stefano; Maisonneuve, Patrick; Viale, Giuseppe; Neri, Antonino

doi:10.1053/hupa.2003.6

Cited by 20 publications

(30 citation statements)

References 36 publications

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“…p21 is activated in a p53-dependent manner and involved in cell cycle arrest. Expression of p21 may also be induced in a p53-independent manner (2,15). p21 can bind PCNA to cause inhibition of DNA replica-tion (2).…”

Section: Discussionmentioning

confidence: 99%

“…The process of tumorigenesis in MM includes the abnormal expression of genes controlling cell cycle progression. Protein p21 (Waf1/Cip1) is an inhibitor of cyclindependent kinases, and therefore plays an important role in cell cycle arrest (15). The cell cycle inhibitory activity of p21 has been correlated with its nuclear localization (2).…”

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confidence: 99%

“…The cell cycle inhibitory activity of p21 has been correlated with its nuclear localization (2). Several studies have evaluated the prognostic significance of p21 in hematopoietic (22,24) and solid (1,7,8,11,13,18,19) tumors, but the prognostic evaluation in MM remains to be explored (6,9,15).…”

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confidence: 99%

“…Multiple myeloma (MM) is a common plasma cell dyscrasia characterized by the uncontrolled expansion of malignant plasma cells (15). The process of tumorigenesis in MM includes the abnormal expression of genes controlling cell cycle progression.…”

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confidence: 99%

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Prognostic implications of p21 (Waf1/Cip1) immunolocalization in multiple myeloma

et al. 2005

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Protein p21 (Waf1/Cip1) plays a critical role in controlling the cell cycle especially as a check point of G1 and is intimately associated with important cellular activities including differentiation, senescence, tumorigenesis, and apoptosis. In the present study, we examined the expression of p21 in multiple myeloma (MM) cells for prognostic evaluation. The immunocytochemical localization of p21 could be categorized into nuclear and cytoplasmic types. The nuclear-type p21 localization was correlated with the severity of MM and the expression of proliferating cell nuclear antigen and p53. Patients with the nuclear-type p21 localization survived significantly shorter than those with the cytoplasmic-type localization. Thus, the present study suggests that p21-immunolocalization can be a useful prognostic marker of MM.

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confidence: 99%

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Prognostic implications of p21 (Waf1/Cip1) immunolocalization in multiple myeloma

et al. 2005

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“…Recent studies revealed that the genetic predisposing factors involved in microsatellite polymorphism (7), single nucleotide polymorphism (SNP) (8,9), methylation (10), mutation as well as deletion (11). Various cytokines such as IL-6, TNF-α, IL-1β and immune regulatory molecules like CTLA-4 (cytotoxic T-lymphocyte antigen-4) as well as proto-oncogene such as p53, p16, nuclear factor IκB, etc., are reported to be the predisposing factors (11)(12)(13)(14)(15). In order to investigate the laboratory diagnostic characters of monoclonal gammopathies in large scale in China as well as to analyze the putative genetic predisposing factors, here in this study, we studied the immunological features of 2,007 cases of monoclonal gammopathies from 10,682 suspected samples for laboratory diagnostic confirmation or exclusion with serum protein electrophoresis (SPE), immunofixation electrophoresis (IFE), immunoglobulin (Ig) quantitation (rate nephelometry) as well as urine free light chain ELISA.…”

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confidence: 99%

Laboratory Characterizations on 2007 Cases of Monoclonal Gammopathies in East China

Wang

Gao

et al. 2008

Cell Mol Immunol

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Primary extramedullary plasmacytoma and multiple myeloma: phenotypic differences revealed by immunohistochemical analysis

Kremer¹,

Ott²,

Nathrath³

et al. 2004

The Journal of Pathology

126

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Primary extramedullary plasmacytomas are infrequent, typically solitary, plasma cell neoplasms that generally pursue an indolent clinical course but may, rarely, convert to multiple myeloma. Phenotypic differences between these two entities are not well defined. Twenty-eight cases of primary extramedullary plasmacytoma and 26 cases of both medullary (n = 17) and extramedullary (n = 9) multiple myeloma were analysed for the expression of proteins known to play a role in the biology of multiple myeloma. Immunohistochemistry was performed on paraffin wax sections using antibodies against cyclin D1, Bcl-2, Bcl-xL, p27, p21, p53, MIB1, CD20, and CD56. Twenty-three extramedullary plasmacytomas were localized in the upper aerodigestive tract, four in the lymph nodes, and one in the testis. There was a strong male predominance (M : F = 6 : 1). None of the patients died from the disease or progressed to multiple myeloma (mean follow-up 50 months). Nine patients developed local relapse and one patient's tumour evolved into a B-cell non-Hodgkin's lymphoma. In contrast to both intra- and extra-medullary multiple myeloma, extramedullary plasmacytoma showed absence of cyclin D1 (p < 0.001) and infrequent expression of CD56 (p < 0.001). Furthermore, extramedullary plasmacytomas were characterized by weaker staining for Bcl-2 protein and rare overexpression of p21 and p53. In comparison to extramedullary multiple myeloma, extramedullary plasmacytoma showed a more mature morphology and lower proliferation indices (p = 0.008). There was no association between the phenotypic parameters investigated and clinical outcome in extramedullary plasmacytoma. In summary, extramedullary plasmacytoma and multiple myeloma show significant immunophenotypic differences, some of which may be of both diagnostic utility and biological relevance.

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Cell cycle regulators in multiple myeloma: Prognostic implications of p53 nuclear accumulation

Cited by 20 publications

References 36 publications

Prognostic implications of p21 (Waf1/Cip1) immunolocalization in multiple myeloma

Prognostic implications of p21 (Waf1/Cip1) immunolocalization in multiple myeloma

Laboratory Characterizations on 2007 Cases of Monoclonal Gammopathies in East China

Primary extramedullary plasmacytoma and multiple myeloma: phenotypic differences revealed by immunohistochemical analysis

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