Miyazaki Kana, Yamaguchi Motoko, Imai Hiroshi, Kobayashi Kyoko, Tamaru Satoshi, Kobayashi Tohru, Shiku Hiroshi, Katayama Naoyuki
Department of Hematology and Oncology, Mie University Graduate School of Medicine, 2-174 Edobashi, Tsu, Mie, 514-8507, Japan,
Int J Hematol. 2015 Aug;102(2):188-94. doi: 10.1007/s12185-015-1812-2. Epub 2015 May 26.
CD5-positive (CD5(+)) diffuse large B-cell lymphoma (DLBCL) has a poor prognosis and high incidence of central nervous system (CNS) relapse, even in the rituximab era. To determine the gene expression profile of CD5(+) DLBCL, total RNA from 90 patients with DLBCL, including 33 CD5(+) DLBCL and 57 CD5-negative (CD5(-)) DLBCL patients, was examined using Agilent human oligo microarrays. These cases were separated into 78 activated B-cell-like (ABC) DLBCLs and 12 germinal center B-cell-like (GCB) DLBCLs. All cases of CD5(+) DLBCL were classified as ABC DLBCLs. The classifier based on gene expression used in a supervised analysis correctly identified CD5 expression in the DLBCL and ABC DLBCL samples. The gene most relevant to CD5 expression was SH3BP5. Enriched GO categories in the CD5(+) ABC DLBCL signature gene set included multicellular organismal signaling, transmission of nerve impulse, and synaptic transmission. The present study, which includes the largest reported number of patients with CD5(+) DLBCL, confirmed that most CD5(+) DLBCLs are ABC DLBCLs, suggesting that therapeutic strategies for ABC DLBCL may be effective for the treatment of CD5(+) DLBCL. Our CD5(+) ABC DLBCL signature gene set may provide insights into the cause of the high frequency of CNS relapse in CD5(+) DLBCL.
即使在利妥昔单抗时代,CD5阳性(CD5(+))弥漫性大B细胞淋巴瘤(DLBCL)的预后也较差,且中枢神经系统(CNS)复发率较高。为了确定CD5(+) DLBCL的基因表达谱,使用安捷伦人类寡核苷酸微阵列检测了90例DLBCL患者的总RNA,其中包括33例CD5(+) DLBCL患者和57例CD5阴性(CD5(-))DLBCL患者。这些病例被分为78例活化B细胞样(ABC)DLBCL和12例生发中心B细胞样(GCB)DLBCL。所有CD5(+) DLBCL病例均被归类为ABC DLBCL。在监督分析中使用的基于基因表达的分类器正确地识别了DLBCL和ABC DLBCL样本中的CD5表达。与CD5表达最相关的基因是SH3BP5。CD5(+) ABC DLBCL特征基因集中富集的GO类别包括多细胞生物体信号传导、神经冲动传递和突触传递。本研究纳入了报道中数量最多的CD5(+) DLBCL患者,证实大多数CD5(+) DLBCL为ABC DLBCL,这表明ABC DLBCL的治疗策略可能对CD5(+) DLBCL的治疗有效。我们的CD5(+) ABC DLBCL特征基因集可能为深入了解CD5(+) DLBCL中枢神经系统复发频率高的原因提供线索。