DNA replication licensing in peripheral B-cell lymphoma

Ellen C. Obermann, Kathryn Leigh Eward, Ahmet Dogan, Elizabeth A. Paul, Marco Loddo, Philippa Munson, Gareth H. Williams, Kai Stoeber

Research output: Contribution to journalArticle

31 Citations (Scopus)

Abstract

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 highgrowth 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.

Original languageEnglish (US)
Pages (from-to)318-328
Number of pages11
JournalJournal of Pathology
Volume205
Issue number3
DOIs
StatePublished - Feb 2005
Externally publishedYes

Fingerprint

Geminin
B-Cell Lymphoma
Licensure
DNA Replication
Lymphoma
Burkitt Lymphoma
Growth
Cell Cycle
B-Lymphocytes
Neoplasms
G2 Phase
G1 Phase
Hematologic Neoplasms
Cell Cycle Checkpoints
Cell Division
Differential Diagnosis
Down-Regulation
Lymphocytes

Keywords

  • B-cell lymphoma
  • DNA replication licensing
  • Geminin
  • Growth fraction
  • Ki67
  • MCM
  • Proliferation

ASJC Scopus subject areas

  • Pathology and Forensic Medicine

Cite this

Obermann, E. C., Eward, K. L., Dogan, A., Paul, E. A., Loddo, M., Munson, P., ... Stoeber, K. (2005). DNA replication licensing in peripheral B-cell lymphoma. Journal of Pathology, 205(3), 318-328. https://doi.org/10.1002/path.1695

DNA replication licensing in peripheral B-cell lymphoma. / Obermann, Ellen C.; Eward, Kathryn Leigh; Dogan, Ahmet; Paul, Elizabeth A.; Loddo, Marco; Munson, Philippa; Williams, Gareth H.; Stoeber, Kai.

In: Journal of Pathology, Vol. 205, No. 3, 02.2005, p. 318-328.

Research output: Contribution to journalArticle

Obermann, EC, Eward, KL, Dogan, A, Paul, EA, Loddo, M, Munson, P, Williams, GH & Stoeber, K 2005, 'DNA replication licensing in peripheral B-cell lymphoma', Journal of Pathology, vol. 205, no. 3, pp. 318-328. https://doi.org/10.1002/path.1695
Obermann EC, Eward KL, Dogan A, Paul EA, Loddo M, Munson P et al. DNA replication licensing in peripheral B-cell lymphoma. Journal of Pathology. 2005 Feb;205(3):318-328. https://doi.org/10.1002/path.1695
Obermann, Ellen C. ; Eward, Kathryn Leigh ; Dogan, Ahmet ; Paul, Elizabeth A. ; Loddo, Marco ; Munson, Philippa ; Williams, Gareth H. ; Stoeber, Kai. / DNA replication licensing in peripheral B-cell lymphoma. In: Journal of Pathology. 2005 ; Vol. 205, No. 3. pp. 318-328.
@article{5886b7cc243a437eb113f30d3c30716f,
title = "DNA replication licensing in peripheral B-cell lymphoma",
abstract = "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 highgrowth 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.",
keywords = "B-cell lymphoma, DNA replication licensing, Geminin, Growth fraction, Ki67, MCM, Proliferation",
author = "Obermann, {Ellen C.} and Eward, {Kathryn Leigh} and Ahmet Dogan and Paul, {Elizabeth A.} and Marco Loddo and Philippa Munson and Williams, {Gareth H.} and Kai Stoeber",
year = "2005",
month = "2",
doi = "10.1002/path.1695",
language = "English (US)",
volume = "205",
pages = "318--328",
journal = "Journal of Pathology",
issn = "0022-3417",
publisher = "John Wiley and Sons Ltd",
number = "3",

}

TY - JOUR

T1 - DNA replication licensing in peripheral B-cell lymphoma

AU - Obermann, Ellen C.

AU - Eward, Kathryn Leigh

AU - Dogan, Ahmet

AU - Paul, Elizabeth A.

AU - Loddo, Marco

AU - Munson, Philippa

AU - Williams, Gareth H.

AU - Stoeber, Kai

PY - 2005/2

Y1 - 2005/2

N2 - 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 highgrowth 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.

AB - 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 highgrowth 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.

KW - B-cell lymphoma

KW - DNA replication licensing

KW - Geminin

KW - Growth fraction

KW - Ki67

KW - MCM

KW - Proliferation

UR - http://www.scopus.com/inward/record.url?scp=13844267473&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=13844267473&partnerID=8YFLogxK

U2 - 10.1002/path.1695

DO - 10.1002/path.1695

M3 - Article

C2 - 15682442

AN - SCOPUS:13844267473

VL - 205

SP - 318

EP - 328

JO - Journal of Pathology

JF - Journal of Pathology

SN - 0022-3417

IS - 3

ER -