1 Ocak 2017 Dergi makalesi Açık Erişim

Hu, Xiaozhou; Baytak, Esra; Li, Jinnan; Akman, Burcu; Okay, Kaan; Hu, Genfu; Scuto, Anna; Zhang, Wenyan; Kucuk, Can

Citation Style Language JSON

{
  "DOI": "10.1016/j.leukres.2017.01.001", 
  "abstract": "Follicular lymphoma (FL) is a common type of indolent lymphoma that occasionally transforms to more aggressive B-cell lymphomas. These transformed follicular lymphomas (tFL) are often associated with chemoresistance whose mechanisms are currently unknown. REL, a proto-oncogene located on frequently amplified 2p16.1-p15 locus, promotes tumorigenesis in many cancer types through deregulation of the NF-KB pathway; however, its role in FL pathobiology or chemoresistance has not been addressed. Here, we evaluated REL gene copy number by q-PCR on FFPE FL tumor samples, and observed REL amplification in 30.4% of FL cases that was associated with weak elevation of transcript levels. PCR-Sanger analysis did not show any somatic mutation in FL tumors. In support of a marginal oncogenic role, a REL-transduced FL cell line was positively selected under limiting serum conditions. Interestingly, reanalysis of previously reported gene expression profiles revealed significant enrichment of DNA damage-induced repair and cell cycle arrest pathways in tFL tumors with high REL expression compared to those with low REL expression consistent with the critical role of c-REL in genotoxicity-induced NF-KB signaling, which was reported to lead to drug resistance. In addition to DNA damage repair genes such as ATM and BRCA1, anti-apoptotic BCL2 was significantly elevated in REL-high FL and tFL tumors. Altogether these data suggest that other genes located in amplified 2p16.1-p15 locus may have more oncogenic role in FL etiology; however, high REL expression may be useful as a predictive biomarker of response to immunochemotherapy, and inhibition of c-REL may potentially sensitize resistant FL or tFL cells to chemotherapy. (C) 2017 Elsevier Ltd. All rights reserved.", 
  "author": [
    {
      "family": "Hu", 
      "given": " Xiaozhou"
    }, 
    {
      "family": "Baytak", 
      "given": " Esra"
    }, 
    {
      "family": "Li", 
      "given": " Jinnan"
    }, 
    {
      "family": "Akman", 
      "given": " Burcu"
    }, 
    {
      "family": "Okay", 
      "given": " Kaan"
    }, 
    {
      "family": "Hu", 
      "given": " Genfu"
    }, 
    {
      "family": "Scuto", 
      "given": " Anna"
    }, 
    {
      "family": "Zhang", 
      "given": " Wenyan"
    }, 
    {
      "family": "Kucuk", 
      "given": " Can"
    }
  ], 
  "container_title": "LEUKEMIA RESEARCH", 
  "id": "43897", 
  "issued": {
    "date-parts": [
      [
        2017, 
        1, 
        1
      ]
    ]
  }, 
  "page": "30-38", 
  "title": "The relationship of REL proto-oncogene to pathobiology and chemoresistance in follicular and transformed follicular lymphoma", 
  "type": "article-journal", 
  "volume": "54"
}