Document Detail

DNA replication licensing in peripheral B-cell lymphoma.
MedLine Citation:
PMID:  15682442     Owner:  NLM     Status:  MEDLINE    
Peripheral B-cell lymphomas representing 90% of lymphoid neoplasms are divided into low- and high-growth fraction lymphomas. Here we investigate regulation of DNA replication licensing during B-cell lymphomagenesis. Combined analysis of origin licensing factors Mcm2 and geminin with the proliferation marker Ki67 in SLL/CLL, MCL, DLBCL and Burkitt lymphoma reveals for the first time the precise cell cycle state of these entities. Given that tight Mcm2 downregulation defines the quiescent state (G0) and that both high- and low-growth fraction lymphomas express Mcm2, the data demonstrate that neoplastic lymphocytes of SLL/CLL and MCL reside in an "in-cycle" G1 state and not in G0 as previously thought. Absence of the S/G2/M phase marker geminin in SLL/CLL and MCL further indicates failure of cell cycle progression in these tumours. In contrast, the high-growth fraction lymphomas DLBCL and Burkitt lymphoma exhibit differential expression of geminin, with the geminin/Ki67 ratio increasing for more aggressive neoplasms in keeping with a shortened G1 phase and thus representing an important discriminator for differential diagnosis. These data provide new insights into abrogation of cell cycle control during B cell lymphomagenesis and suggest that combined analysis of origin licensing factors may contribute to improved treatment decisions and prognosis in haematopoietic malignancies.
Ellen C Obermann; Kathryn Leigh Eward; Ahmet Dogan; Elizabeth A Paul; Marco Loddo; Philippa Munson; Gareth H Williams; Kai Stoeber
Publication Detail:
Type:  Journal Article    
Journal Detail:
Title:  The Journal of pathology     Volume:  205     ISSN:  0022-3417     ISO Abbreviation:  J. Pathol.     Publication Date:  2005 Feb 
Date Detail:
Created Date:  2005-02-03     Completed Date:  2005-03-02     Revised Date:  2007-11-15    
Medline Journal Info:
Nlm Unique ID:  0204634     Medline TA:  J Pathol     Country:  England    
Other Details:
Languages:  eng     Pagination:  318-28     Citation Subset:  IM    
Department of Histopathology, University College London, Rockefeller Building, University Street, London, WC1E 6JJ, United Kingdom.
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MeSH Terms
Cell Cycle
Cell Cycle Proteins / metabolism
Cell Transformation, Neoplastic / pathology
DNA Replication*
DNA, Neoplasm / genetics*
Diagnosis, Differential
Flow Cytometry / methods
Ki-67 Antigen / metabolism
Leukemia, Lymphocytic, Chronic, B-Cell / metabolism
Lymphoma, B-Cell / diagnosis,  genetics,  metabolism,  pathology*
Neoplasm Proteins / metabolism
Nuclear Proteins / metabolism
Tumor Cells, Cultured
Tumor Markers, Biological / metabolism
Reg. No./Substance:
0/Cell Cycle Proteins; 0/DNA, Neoplasm; 0/GMNN protein, human; 0/Ki-67 Antigen; 0/MCM2 protein, human; 0/Neoplasm Proteins; 0/Nuclear Proteins; 0/Tumor Markers, Biological

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