title: Loss of PRDM1/BLIMP-1 function contributes to poor prognosis of activated B-cell-like diffuse large B-cell lymphoma.
abstract: 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.
authors: Department of Hematopathology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.|The First Affiliated Hospital of Nanjing Medical University, Jiangsu Province Hospital, Nanjing, China.
authors: Y
authors: Y
authors: Xia
authors: Department of Hematopathology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
authors: Z Y
authors: ZY
authors: Xu-Monette
authors: University Hospital, Basel, Switzerland.
authors: A
authors: A
authors: Tzankov
authors: Department of Hematopathology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
authors: X
authors: X
authors: Li
authors: Department of Bioinformatics and Computational Biology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
authors: G C
authors: GC
authors: Manyam
authors: Columbia University Medical Center and New York Presbyterian Hospital, New York, NY, USA.
authors: V
authors: V
authors: Murty
authors: Columbia University Medical Center and New York Presbyterian Hospital, New York, NY, USA.
authors: G
authors: G
authors: Bhagat
authors: Department of Hematopathology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
authors: S
authors: S
authors: Zhang
authors: Columbia University Medical Center and New York Presbyterian Hospital, New York, NY, USA.
authors: L
authors: L
authors: Pasqualucci
authors: San Bortolo Hospital, Vicenza, Italy.
authors: C
authors: C
authors: Visco
authors: Aalborg University Hospital, Aalborg, Denmark.
authors: K
authors: K
authors: Dybkaer
authors: Memorial Sloan-Kettering Cancer Center, New York, NY, USA.
authors: A
authors: A
authors: Chiu
authors: Weill Medical College of Cornell University, New York, NY, USA.
authors: A
authors: A
authors: Orazi
authors: The Methodist Hospital, Houston, TX, USA.
authors: Y
authors: Y
authors: Zu
authors: Cornell University, Ithaca, NY, USA.
authors: K L
authors: KL
authors: Richards
authors: Cleveland Clinic, Cleveland, OH, USA.
authors: E D
authors: ED
authors: Hsi
authors: University of Hong Kong Li Ka Shing Faculty of Medicine, Hong Kong, China.
authors: W W L
authors: WW
authors: Choi
authors: Radboud University Nijmegen Medical Centre, Nijmegen, Netherlands.
authors: J H
authors: JH
authors: van Krieken
authors: Asan Medical Center, Ulsan University College of Medicine, Seoul, South Korea.
authors: J
authors: J
authors: Huh
authors: San Raffaele H. Scientific Institute, Milan, Italy.
authors: M
authors: M
authors: Ponzoni
authors: San Raffaele H. Scientific Institute, Milan, Italy.
authors: A J M
authors: AJ
authors: Ferreri
authors: Odense University Hospital, Odense, Denmark.
authors: M B
authors: MB
authors: Møller
authors: Gundersen Lutheran Health System, La Crosse, WI, USA.
authors: B M
authors: BM
authors: Parsons
authors: Feinberg School of Medicine, Northwestern University, Chicago, IL, USA.
authors: J N
authors: JN
authors: Winter
authors: Hospital Universitario Marqués de Valdecilla, Santander, Spain.
authors: M A
authors: MA
authors: Piris
authors: Department of Lymphoma/Myeloma, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
authors: J
authors: J
authors: Westin
authors: Department of Lymphoma/Myeloma, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
authors: N
authors: N
authors: Fowler
authors: Department of Hematopathology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
authors: R N
authors: RN
authors: Miranda
authors: Department of Hematopathology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
authors: C Y
authors: CY
authors: Ok
authors: Department of Cancer Biology, Lerner Research Institute, Cleveland Clinic, Cleveland, OH, USA.
authors: Y
authors: Y
authors: Li
authors: The First Affiliated Hospital of Nanjing Medical University, Jiangsu Province Hospital, Nanjing, China.
authors: J
authors: J
authors: Li
authors: Department of Hematopathology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
authors: L J
authors: LJ
authors: Medeiros
authors: Department of Hematopathology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.|The University of Texas School of Medicine, Graduate School of Biomedical Sciences, Houston, TX, USA.
authors: K H
authors: KH
authors: Young
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use; D014408:Biomarkers, Tumor; D001706:Biopsy; D005260:Female; D005500:Follow-Up Studies; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D016403:Lymphoma, Large B-Cell, Diffuse / Q000175:diagnosis / Q000188:drug therapy / Q000235:genetics* / Q000401:mortality*; D008297:Male; D008875:Middle Aged; D009154:Mutation; D009367:Neoplasm Staging; D000074462:Positive Regulatory Domain I-Binding Factor 1; D011379:Prognosis; D012097:Repressor Proteins / Q000235:genetics* / Q000378:metabolism; D017384:Sequence Deletion; D059467:Transcriptome; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: D014408:Biomarkers, Tumor; D012097:Repressor Proteins; C087042:PRDM1 protein, human; D000074462:Positive Regulatory Domain I-Binding Factor 1