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DNMT1 is predictive of survival and associated with Ki-67 expression in R-CHOP-treated diffuse large B-cell lymphomas

Abstract:
DNMT1 is a target of approved anti-cancer drugs including decitabine. However, the prognostic value of DNMT1 protein expression in R-CHOP-treated diffuse large B-cell lymphomas (DLBCLs) remains unexplored. Here we showed that DNMT1 was expressed in the majority of DLBCL cases (n = 209/230, 90.9%) with higher expression in germinal centre B-cell-like (GCB)-DLBCL subtype. Low and negative DNMT1 expression (20% cut-off, n = 33/230, 14.3%) was predictive of worse overall survival (OS; p < 0.001) and progression-free survival (PFS; p < 0.001). Nonetheless, of the 209 DNMT1 positive patients, 33% and 42% did not achieve 5-year OS and PFS, respectively, indicating that DNMT1 positive patients showed considerably heterogeneous outcomes. Moreover, DNMT1 was frequently expressed in mitotic cells and significantly correlated with Ki-67 or BCL6 expression (r = 0.60 or 0.44, respectively; p < 0.001). We demonstrate that DNMT1 is predictive of DLBCL patients' survival, and suggest that DNMT1 could be a DLBCL therapeutic target due to its significant association with Ki-67.
Publication status:
Published
Peer review status:
Peer reviewed

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Publisher copy:
10.1016/j.pathol.2017.08.009

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Role:
Author
ORCID:
0000-0002-4558-1967
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Institution:
University of Oxford
Division:
Medical Sciences Division
Department:
RDM; RDM Clinical Laboratory Sciences
Role:
Author
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Role:
Author
ORCID:
0000-0003-0324-2251


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Funding agency for:
Banham, AH
Grant:
Programme grant (13047
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Funding agency for:
Lawrie, CH
Grant:
PIE13/00048
Proyectos integrados de excelencia
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Funding agency for:
Lawrie, CH
Grant:
Proyectos integrados de excelencia
PIE13/00048
More from this funder
Funding agency for:
Lawrie, CH
Grant:
Proyectos integrados de excelencia
PIE13/00048
More from this funder
Grant:
Short Term (304/PPSP/61312002


Publisher:
Elsevier
Journal:
Pathology More from this journal
Volume:
49
Issue:
7
Pages:
731-739
Publication date:
2017-10-23
Acceptance date:
2017-08-20
DOI:
EISSN:
1465-3931
ISSN:
0031-3025


Keywords:
Pubs id:
pubs:809872
UUID:
uuid:f5b74a28-1c4d-45f8-9d2f-64cb670d8fc8
Local pid:
pubs:809872
Source identifiers:
809872
Deposit date:
2018-01-10

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