title: Activation of the polycomb repressive complex pathway in the bone marrow resident cells of diffuse large B-cell lymphoma patients.
abstract: The present study investigated the activation of polycomb repressive complex 2 (PRC2) pathway proteins in the resident cells within the bone marrow hematopoietic microenvironment of diffuse large B-cell lymphoma (DLBCL) patients. PRC2 proteins (enhancer of zeste homolog 2, suppressor of zeste 12 homolog, and embryonic ectoderm development), histone methylation mark (H3K27me3), and c-MYC activation were evaluated in pretreatment bone marrow from 208 DLBLC patients. Positive expression of the PRC2, H3K27me3, and c-MYC in the bone marrow resident cells was more frequent in cases with bone marrow involvement of tumor. The expression among PRC2, H3K27me3 mark, and c-MYC was closely correlated. Positive PRC2 expression in bone marrow resident cells was significantly associated with inferior progression-free survival (PFS) and overall survival (OS) and determined to be an independent prognostic factor of inferior PFS and OS. In conclusion, the PRC pathway was frequently activated in bone marrow resident cells of DLBCL patients, and PRC activation was tumor-related and associated with poor clinical outcomes.
authors.affiliation: a Department of Pathology , Yonsei University College of Medicine , Seoul , Korea.
authors.forename: Eun Ji
authors.initials: EJ
authors.lastname: Oh
authors.affiliation: a Department of Pathology , Yonsei University College of Medicine , Seoul , Korea.
authors.forename: Eun Kyung
authors.initials: EK
authors.lastname: Kim
authors.affiliation: a Department of Pathology , Yonsei University College of Medicine , Seoul , Korea.
authors.forename: Woo Ick
authors.initials: WI
authors.lastname: Yang
authors.affiliation: a Department of Pathology , Yonsei University College of Medicine , Seoul , Korea.
authors.forename: Sun Och
authors.initials: SO
authors.lastname: Yoon
mesh_terms: D000328:Adult; D000368:Aged; D001706:Biopsy; D001853:Bone Marrow / Q000473:pathology; D001854:Bone Marrow Cells / Q000378:metabolism*; D002467:Cell Nucleus / Q000378:metabolism; D018572:Disease-Free Survival; D000071221:Enhancer of Zeste Homolog 2 Protein / Q000378:metabolism*; D005260:Female; D006657:Histones / Q000378:metabolism; D006801:Humans; D016403:Lymphoma, Large B-Cell, Diffuse / Q000401:mortality / Q000473:pathology*; D008297:Male; D008745:Methylation; D008875:Middle Aged; D009363:Neoplasm Proteins; D063151:Polycomb Repressive Complex 2 / Q000378:metabolism*; D011379:Prognosis; D016271:Proto-Oncogene Proteins c-myc / Q000378:metabolism; D015398:Signal Transduction; D014157:Transcription Factors; D059016:Tumor Microenvironment
chemical_list: C491488:EED protein, human; D006657:Histones; D009363:Neoplasm Proteins; D016271:Proto-Oncogene Proteins c-myc; C430461:SUZ12 protein, human; D014157:Transcription Factors; C498409:EZH2 protein, human; D000071221:Enhancer of Zeste Homolog 2 Protein; D063151:Polycomb Repressive Complex 2
keywords: Bone marrow; c-MYC; diffuse; histone H3 trimethylation at lysine 27; large B cell; lymphoma; polycomb repressive complex 2