Loss of PRDM1/BLIMP-1 function contributes to poor prognosis of activated B-cell-like diffuse large B-cell lymphoma.

Xia, Y

Xu-Monette, ZY

Tzankov, A

Li, X

Manyam, GC

Murty, V

Bhagat, G

Zhang, S

Pasqualucci, L

Visco, C

Dybkaer, K

Chiu, A

Orazi, A

Zu, Y

Richards, KL

Hsi, ED

Choi, WWL

van Krieken, JH

Huh, J

Ponzoni, M

Ferreri, AJM

Møller, MB

Parsons, BM

Winter, JN

Piris, MA

Westin, J

Fowler, N

Miranda, RN

Ok, CY

Li, Y

Li, J

Medeiros, LJ

Young, KH

2019-09-21T21:12:20Z

2019-09-21T21:12:20Z

2017-03

2019-09-21T21:12:19Z

PRDM1/BLIMP-1, a master regulator of plasma-cell differentiation, is frequently inactivated in activated B-cell-like (ABC) diffuse large B-cell lymphoma (DLBCL) patients. Little is known about its genetic aberrations and relevant clinical implications. A large series of patients with de novo DLBCL was effectively evaluated for PRDM1/BLIMP-1 deletion, mutation, and protein expression. BLIMP-1 expression was frequently associated with the ABC phenotype and plasmablastic morphologic subtype of DLBCL, yet 63% of the ABC-DLBCL patients were negative for BLIMP-1 protein expression. In these patients, loss of BLIMP-1 was associated with Myc overexpression and decreased expression of p53 pathway molecules. In addition, homozygous PRDM1 deletions and PRDM1 mutations within exons 1 and 2, which encode for domains crucial for transcriptional repression, were found to show a poor prognostic impact in patients with ABC-DLBCL but not in those with germinal center B-cell-like DLBCL (GCB-DLBCL). Gene expression profiling revealed that loss of PRDM1/BLIMP-1 expression correlated with a decreased plasma-cell differentiation signature and upregulation of genes involved in B-cell receptor signaling and tumor-cell proliferation. In conclusion, these results provide novel clinical and biological insight into the tumor-suppressive role of PRDM1/BLIMP-1 in ABC-DLBCL patients and suggest that loss of PRDM1/BLIMP-1 function contributes to the overall poor prognosis of ABC-DLBCL patients.

leu2016243

0887-6924

1476-5551

https://hdl.handle.net/10161/19331

eng

Springer Science and Business Media LLC

Leukemia

10.1038/leu.2016.243

Humans

Repressor Proteins

Antineoplastic Combined Chemotherapy Protocols

Biopsy

Neoplasm Staging

Prognosis

Treatment Outcome

Follow-Up Studies

Gene Expression Profiling

Gene Expression Regulation, Neoplastic

Sequence Deletion

Mutation

Adolescent

Adult

Aged

Aged, 80 and over

Middle Aged

Female

Male

Lymphoma, Large B-Cell, Diffuse

Young Adult

Transcriptome

Biomarkers, Tumor

Positive Regulatory Domain I-Binding Factor 1

Loss of PRDM1/BLIMP-1 function contributes to poor prognosis of activated B-cell-like diffuse large B-cell lymphoma.

Journal article

Xu-Monette, ZY|0000-0002-7615-3949

Young, KH|0000-0002-5755-8932

625

636

3

School of Medicine

Duke

Pathology

Clinical Science Departments

Published

31