Transient expression of Bcl6 is sufficient for oncogenic function and induction of mature B-cell lymphoma.
Transient expression of Bcl6 is sufficient for oncogenic function and induction of mature B-cell lymphoma.
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DOI：
10.1038/ncomms4904
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发表时间：
2014-06-02
影响因子：
16.6
通讯作者：
Sanchez-Garcia, Isidro
中科院分区：
文献类型：
--
作者：
Green, Michael R.;Vicente-Duenas, Carolina;Romero-Camarero, Isabel;Liu, Chih Long;Dai, Bo;Gonzalez-Herrero, Ines;Garcia-Ramirez, Idoia;Alonso-Escudero, Esther;Iqbal, Javeed;Chan, Wing C.;Campos-Sanchez, Elena;Orfao, Alberto;Pintado, Belen;Flores, Teresa;Blanco, Oscar;Jimenez, Rafael;Angel Martinez-Climent, Jose;Garcia Criado, Francisco Javier;Garcia Cenador, Maria Begona;Zhao, Shuchun;Natkunam, Yasodha;Lossos, Izidore S.;Majeti, Ravindra;Melnick, Ari;Cobaleda, Cesar;Alizadeh, Ash A.;Sanchez-Garcia, Isidro
弥漫性大 B 细胞淋巴瘤 (DLBCL) 是最常见的淋巴瘤，可根据与生发中心 B 细胞（GCB 样）或活化 B 细胞（ABC 样）相似的分子特征分为两种亚型。在这里，我们确定 3q27.2 的增益与 DLBCL 的不良结局显着相关，并与 ABC 样亚型相关。该病变包括 BCL6 癌基因，但不会改变 BCL6 转录水平或靶基因抑制。另外，我们鉴定了 BCL6 在人类造血干/祖细胞 (HSPC) 子集中的表达。因此，我们假设 BCL6 可能通过肇事逃逸的致癌作用发挥作用。我们通过在小鼠 HSPC 中瞬时表达 Bcl6 来对此进行建模，发现它会导致缺乏 Bcl6 表达和靶基因抑制的成熟 B 细胞淋巴瘤，在转录上与 GCB 后细胞相似，并显示出从 HSPC 到成熟 B 细胞保守的表观遗传变化。这些结果共同表明，Bcl6 可能在淋巴瘤发生中发挥肇事逃逸的作用。
Diffuse large B-cell lymphoma (DLBCL) is the most common lymphoma and can be separated into two subtypes based upon molecular features with similarities to germinal center B-cells (GCB-like) or activated B-cells (ABC-like). Here we identify gain of 3q27.2 as being significantly associated with adverse outcome in DLBCL and linked with the ABC-like subtype. This lesion includes the BCL6 oncogene, but does not alter BCL6 transcript levels or target-gene repression. Separately, we identify expression of BCL6 in a subset of human hematopoietic stem/progenitor cells (HSPCs). We therefore hypothesize that BCL6 may act by hit-and-run oncogenesis. We model this by transiently expressing Bcl6 within murine HSPCs, and find it causes mature B-cell lymphomas that lack Bcl6 expression and target-gene repression, are transcriptionally similar to post-GCB cells, and show epigenetic changes that are conserved from HSPCs to mature B-cells. Together these results suggest that Bcl6 may function in a hit-and-run role in lymphomagenesis.
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影响因子：
20.3
作者：
Basso, Katia;Saito, Masumichi;Dalla-Favera, Riccardo
通讯作者：
Dalla-Favera, Riccardo
影响因子：
56.9
作者：
Jain, M;Arvanitis, C;Felsher, DW
通讯作者：
Felsher, DW
影响因子：
20.3
作者：
Green, Michael R.;Monti, Stefano;Shipp, Margaret A.
通讯作者：
Shipp, Margaret A.
影响因子：
20.3
作者：
Cerchietti, Leandro C.;Yang, Shao Ning;Melnick, Ari
通讯作者：
Melnick, Ari
影响因子：
3.7
作者：
Green, Michael R.;Aya-Bonilla, Carlos;Griffiths, Lyn R.
通讯作者：
Griffiths, Lyn R.