Journal article
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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(Preview, Accepted manuscript, pdf, 8.9MB, Terms of use)
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- Publisher copy:
- 10.1016/j.pathol.2017.08.009
Authors
+ Diputación Foral de Gipuzkoa
More from this funder
- Funding agency for:
- Lawrie, CH
- Grant:
- PIE13/00048
- Proyectos integrados de excelencia
+ Instituto de salud Carlos II
More from this funder
- Funding agency for:
- Lawrie, CH
- Grant:
- Proyectos integrados de excelencia
- PIE13/00048
+ Ikerbasque - Basque Foundation for Science
More from this funder
- Funding agency for:
- Lawrie, CH
- Grant:
- Proyectos integrados de excelencia
- PIE13/00048
- 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:
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1465-3931
- ISSN:
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0031-3025
- Keywords:
- Pubs id:
-
pubs:809872
- UUID:
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uuid:f5b74a28-1c4d-45f8-9d2f-64cb670d8fc8
- Local pid:
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pubs:809872
- Source identifiers:
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809872
- Deposit date:
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2018-01-10
Terms of use
- Copyright holder:
- Crown Copyright
- Copyright date:
- 2017
- Notes:
-
Crown Copyright © 2017 Published by Elsevier B.V. on behalf of Royal College of Pathologists of
Australasia. This is the accepted manuscript version of the article. The final version is available online from Elsevier at: https://doi.org/10.1016/j.pathol.2017.08.009
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