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

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DNMT1 is predictive of survival and associated with Ki-67 expression in R-CHOP-treated diffuse large B-cell lymphomas. / Loo, Suet Kee; Ch'ng, Ewe Seng; Lawrie, Charles H; Muruzabal, María Arestin; Gaafar, Ayman; Pomposo, María Puente; Husin, Azlan; Md Salleh, Md Salzihan; Banham, Alison H; Pedersen, Lars M; Møller, Michael B; Green, Tina M; Wong, Kah Keng.

In: Pathology, Vol. 49, No. 7, 2017, p. 731-739.

Research output: Contribution to journal › Journal article › Research › peer-review

Harvard

Loo, SK, Ch'ng, ES, Lawrie, CH, Muruzabal, MA, Gaafar, A, Pomposo, MP, Husin, A, Md Salleh, MS, Banham, AH, Pedersen, LM, Møller, MB, Green, TM & Wong, KK 2017, 'DNMT1 is predictive of survival and associated with Ki-67 expression in R-CHOP-treated diffuse large B-cell lymphomas', Pathology, vol. 49, no. 7, pp. 731-739. https://doi.org/10.1016/j.pathol.2017.08.009

APA

Loo, S. K., Ch'ng, E. S., Lawrie, C. H., Muruzabal, M. A., Gaafar, A., Pomposo, M. P., Husin, A., Md Salleh, M. S., Banham, A. H., Pedersen, L. M., Møller, M. B., Green, T. M., & Wong, K. K. (2017). DNMT1 is predictive of survival and associated with Ki-67 expression in R-CHOP-treated diffuse large B-cell lymphomas. Pathology, 49(7), 731-739. https://doi.org/10.1016/j.pathol.2017.08.009

Vancouver

Loo SK, Ch'ng ES, Lawrie CH, Muruzabal MA, Gaafar A, Pomposo MP et al. DNMT1 is predictive of survival and associated with Ki-67 expression in R-CHOP-treated diffuse large B-cell lymphomas. Pathology. 2017;49(7):731-739. https://doi.org/10.1016/j.pathol.2017.08.009

Author

Loo, Suet Kee ; Ch'ng, Ewe Seng ; Lawrie, Charles H ; Muruzabal, María Arestin ; Gaafar, Ayman ; Pomposo, María Puente ; Husin, Azlan ; Md Salleh, Md Salzihan ; Banham, Alison H ; Pedersen, Lars M ; Møller, Michael B ; Green, Tina M ; Wong, Kah Keng. / DNMT1 is predictive of survival and associated with Ki-67 expression in R-CHOP-treated diffuse large B-cell lymphomas. In: Pathology. 2017 ; Vol. 49, No. 7. pp. 731-739.

Bibtex

@article{f99c607d01f9497e87aff83204fb8c2b,

title = "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.",

keywords = "Adult, Aged, Aged, 80 and over, Antibodies, Monoclonal, Murine-Derived, Antineoplastic Combined Chemotherapy Protocols, B-Lymphocytes/pathology, Biomarkers, Tumor/metabolism, Cyclophosphamide, DNA (Cytosine-5-)-Methyltransferase 1/metabolism, Disease-Free Survival, Doxorubicin, Female, Germinal Center/pathology, Humans, Ki-67 Antigen/metabolism, Lymphoma, Large B-Cell, Diffuse/diagnosis, Male, Middle Aged, Prednisone, Prognosis, Vincristine, Young Adult",

author = "Loo, {Suet Kee} and Ch'ng, {Ewe Seng} and Lawrie, {Charles H} and Muruzabal, {Mar{\'i}a Arestin} and Ayman Gaafar and Pomposo, {Mar{\'i}a Puente} and Azlan Husin and {Md Salleh}, {Md Salzihan} and Banham, {Alison H} and Pedersen, {Lars M} and M{\o}ller, {Michael B} and Green, {Tina M} and Wong, {Kah Keng}",

year = "2017",

doi = "10.1016/j.pathol.2017.08.009",

language = "English",

volume = "49",

pages = "731--739",

journal = "Pathology",

issn = "0031-3025",

publisher = "Lippincott Williams & Wilkins, Ltd.",

number = "7",

}

RIS

TY - JOUR

T1 - DNMT1 is predictive of survival and associated with Ki-67 expression in R-CHOP-treated diffuse large B-cell lymphomas

AU - Loo, Suet Kee

AU - Ch'ng, Ewe Seng

AU - Lawrie, Charles H

AU - Muruzabal, María Arestin

AU - Gaafar, Ayman

AU - Pomposo, María Puente

AU - Husin, Azlan

AU - Md Salleh, Md Salzihan

AU - Banham, Alison H

AU - Pedersen, Lars M

AU - Møller, Michael B

AU - Green, Tina M

AU - Wong, Kah Keng

PY - 2017

Y1 - 2017

N2 - 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.

AB - 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.

KW - Adult

KW - Aged

KW - Aged, 80 and over

KW - Antibodies, Monoclonal, Murine-Derived

KW - Antineoplastic Combined Chemotherapy Protocols

KW - B-Lymphocytes/pathology

KW - Biomarkers, Tumor/metabolism

KW - Cyclophosphamide

KW - DNA (Cytosine-5-)-Methyltransferase 1/metabolism

KW - Disease-Free Survival

KW - Doxorubicin

KW - Female

KW - Germinal Center/pathology

KW - Humans

KW - Ki-67 Antigen/metabolism

KW - Lymphoma, Large B-Cell, Diffuse/diagnosis

KW - Male

KW - Middle Aged

KW - Prednisone

KW - Prognosis

KW - Vincristine

KW - Young Adult

U2 - 10.1016/j.pathol.2017.08.009

DO - 10.1016/j.pathol.2017.08.009

M3 - Journal article

C2 - 29074044

VL - 49

SP - 731

EP - 739

JO - Pathology

JF - Pathology

SN - 0031-3025

IS - 7

ER -

ID: 197002467

Forskning