title: [Potential mechanism and prognostic value of promoter methylation of PRDM1 gene in diffuse large B cell lymphoma].
abstract: Objective:To investigate PRDM1 gene methylation status, immune classification and their prognostic significance in diffuse large B cell lymphoma (DLBCL).Methods:Immunohistochemical (IHC) staining for CD20, CD10, bcl-2, bcl-6, PRDM1/Blimp-1 and MUM1 was carried out in 100 cases of DLBCL specimens and 20 reactive lymphoid proliferation samples. All patients were classified into germinal center B cell-like (GCB) and activated B cell-like (ABC) subtype according to Hans' algorithmin. PRDM1 gene methylation was detected by methylation-specific PCR (MSP) and its relationship with clinicopathologic parameters was analyzed. OCI-Ly1 (GCB type) and OCI-Ly3 (ABC type) cell lines were transfected by Small interfering RNA(siRNA) with cationic lipid reagent transfection mediated, and the PRDM1/Blimp-1 expression in before and after transfected cell lines were detected with reverse transcription-PCR and Western blot methods. The relationship between PRDM1 gene methylation, clinicopathologic parameter and survival was analyzed using one-way analysis of variance.Results:One hundred patients were classified into 73 (73%) cases of GCB subtypes and 27 (27%) cases of ABC. PRDM1/Blimp-1 was expressed in 21 DLBCL and highly expressed in 20 reactive lymphoid proliferation. PRDM1 gene methylation was detected in 23% (23/100) of DLBCL, while no methylation was detected in all 20 reactive lymphoid proliferation. The difference of the PRDM1 methylation status between DLBCL and the control samples was statistically significant (P=0.004). However, there was no significant correlation between the PRDM1 gene methylation and clinicopathologic parameters (P>0.05). Reverse transcription-PCR and Western blot showed that PRDM1 gene expression was reduced in siRNA-induced group compared with blank control group and negative control group. One-way analysis of variance revealed that aged ≥60 years, performance status score above 3, and the presence of general symptoms were associated with significantly lower overall survival rate.Conclusions:PRDM1 gene silencing with aberrant CpG methylation is probably one of the critical events in the oncogenesis of DLBCL. This may have important implications as a candidate marker for diagnosis and targeted gene therapy. Meanwhile in vitro siRNA transfected OCI-Ly1 and OCI-Ly3 cell lines confirm that PRDM1 gene is a suppressor gene in DLBCL and may represent a novel therapeutic target.
authors.affiliation: Department of Pathology, the First Affiliated Hospital of Xinjiang Medical University, Urumqi 830054, China.
authors.forename: X Y
authors.initials: XY
authors.lastname: Zhang
authors.forename: Z P
authors.initials: ZP
authors.lastname: Ma
authors.forename: W L
authors.initials: WL
authors.lastname: Cui
authors.forename: R
authors.initials: R
authors.lastname: Chen
authors.forename: Abulajiang
authors.initials: A
authors.lastname: Glinaer
authors.forename: N
authors.initials: N
authors.lastname: Miao
authors.forename: X X
authors.initials: XX
authors.lastname: Li
mesh_terms: D000704:Analysis of Variance; D018951:Antigens, CD20 / Q000378:metabolism; D001402:B-Lymphocytes; D019175:DNA Methylation; D005260:Female; D020868:Gene Silencing; D018858:Germinal Center; D006801:Humans; D016403:Lymphoma, Large B-Cell, Diffuse / Q000235:genetics* / Q000378:metabolism / Q000401:mortality; D008297:Male; D015260:Neprilysin / Q000378:metabolism; D000074462:Positive Regulatory Domain I-Binding Factor 1; D011379:Prognosis; D011401:Promoter Regions, Genetic; D051560:Proto-Oncogene Proteins c-bcl-6 / Q000235:genetics / Q000378:metabolism; D012097:Repressor Proteins / Q000235:genetics* / Q000378:metabolism; D015996:Survival Rate; D014157:Transcription Factors
chemical_list: D018951:Antigens, CD20; C084103:BCL6 protein, human; D051560:Proto-Oncogene Proteins c-bcl-6; D012097:Repressor Proteins; D014157:Transcription Factors; C087042:PRDM1 protein, human; D000074462:Positive Regulatory Domain I-Binding Factor 1; D015260:Neprilysin