The molecular signature of mediastinal large B-cell lymphoma differs from that of other diffuse large B-cell lymphomas and shares features with classical Hodgkin lymphoma
The molecular signature of mediastinal large B-cell lymphoma differs from that of other diffuse large B-cell lymphomas and shares features with classical Hodgkin lymphoma
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DOI：
10.1182/blood-2003-06-1841
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发表时间：
2003-12-01
期刊：
影响因子：
20.3
通讯作者：
Shipp, MA
中科院分区：
文献类型：
--
作者：
Savage, KJ;Monti, S;Shipp, MA
纵隔大 B 细胞淋巴瘤 (MLBCL) 是最近发现的弥漫性大 B 细胞淋巴瘤 (DLBCL) 的一种亚型，其特征为年轻女性患者中的局限性肿瘤。尽管 MLBCL 具有独特的病理特征，但其临床上类似于经典霍奇金淋巴瘤 (cHL) 的结节性硬化亚型。为了阐明 MLBCL 的分子特征，我们比较了新诊断的 MLBCL 和 DLBCL 的基因表达谱，并开发了这些疾病的分类器。 MLBCL 的 B 细胞受体信号级联多个成分的表达水平较低，其特征类似于 cHL 的 Reed-Sternberg 细胞。与 cHL 一样，MLBCL 也高水平表达白细胞介素 13 (IL-13) 受体和 IL-13 信号下游效应器（Janus 激酶 2 [JAK2] 和信号转导器和转录激活剂 1 [STAT1]）、肿瘤坏死因子 (TNF) 家族成员和 TNF 受体相关因子 1 (TRAF1)。免疫组织化学证实 MLBCL 中 STAT1 和 TRAF1 表达增加。鉴于 TRAF1 表达和已知与核因子 kappaB (NF-kappaB) 的联系，还评估了 MLBCL 的 c-REL 蛋白核转位。在几乎所有情况下，c-REL 都定位于细胞核，与 NF-kappaB 通路的激活一致。这些研究确定了 MLBCL 和 cHL 之间的分子联系以及共同的生存途径。 (C) 2003 年，美国血液学会。
Mediastinal large B-cell lymphoma (MLBCL) is a recently identified subtype of diffuse large B-cell lymphoma (DLBCL) that characteristically presents as localized tumors in young female patients. Although MLBCL has distinctive pathologic features, it clinically resembles the nodular sclerosis subtype of classical Hodgkin lymphoma (cHL). To elucidate the molecular features of MLBCL, we compared the gene expression profiles of newly diagnosed MLBCL and DLBCL and developed a classifier of these diseases. MLBCLs had low levels of expression of multiple components of the B-cell receptor signaling cascade, a profile resembling that of Reed-Sternberg cells of cHL. Like cHLs, MLBCLs also had high levels of expression of the interleukin-13 (IL-13) receptor and downstream effectors of IL-13 signaling (Janus kinase-2 [JAK2] and signal transducer and activator of transcription-1 [STAT1]), tumor necrosis factor (TNF) family members, and TNF receptor-associated factor-1 (TRAF1). Increased expression of STAT1 and TRAF1 in MLBCL was confirmed by immunohistochemistry. Given the TRAF1 expression and known link to nuclear factor-kappaB (NF-kappaB), MLBCLs were also evaluated for nuclear translocation of c-REL protein. In almost all cases, c-REL was localized to the nucleus, consistent with activation of the NF-kappaB pathway. These studies identify a molecular link between MLBCL and cHL and a shared survival pathway. (C) 2003 by The American Society of Hematology.