B-cell receptor signaling in diffuse large B-cell lymphoma.
B-cell receptor signaling in diffuse large B-cell lymphoma.
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DOI：
10.1053/j.seminhematol.2015.01.008
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发表时间：
2015-04
影响因子：
3.6
通讯作者：
Staudt LM
中科院分区：
文献类型：
--
作者：
Young RM;Shaffer AL 3rd;Phelan JD;Staudt LM
最近针对BCR通路的药物的临床成功强调了理解弥漫大B细胞淋巴瘤（DLBCL）中B细胞受体（BCR）生存信号传导的遗传和生化基础的重要性。DLBCL由多种不同的分子亚型组成，具有不同的临床结果。活化的B细胞样（ABC）亚型是DLBCL最具侵袭性的形式，通常对标准化疗具有耐药性。ABC DLBCL表达抗原活化B细胞中发现的许多基因，遗传学和药理学研究表明，ABC DLBCL肿瘤对NF-κB活性有依赖性。这种NF-κB活性的起源一直不清楚，直到RNA干扰筛选确定大多数ABC DLBCL细胞系依赖于BCR成分和下游信号效应物的表达来激活NF-κB。布鲁顿酪氨酸激酶（Btk）是BCR信号参与NF-κB所需的激酶，伊鲁替尼对ABC DLBCL肿瘤具有选择性毒性；这一发现现在已经被应用于临床。这些新的靶点不仅为ABC DLBCL提供了一个有希望的新治疗选择，而且也证明了对致癌信号通路的深入分子理解的价值。
The importance of understanding the genetic and biochemical basis of B cell receptor (BCR) survival signaling in diffuse large B cell lymphoma (DLBCL) is underscored by the recent clinical success of agents that target the BCR pathway. DLBCL is composed of multiple distinct molecular subtypes with divergent clinical outcomes. The activated B cell-like (ABC) subtype is the most aggressive form of DLBCL and is often resistant to standard chemotherapies. ABC DLBCL expresses numerous genes found in antigen-activated B cells, and genetic and pharmacologic studies have demonstrated that ABC DLBCL tumors are addicted to NF-κB activity. The origins of this NF-κB activity remained obscure until RNA interference screens established that the majority of ABC DLBCL cell lines rely on expression of BCR components and downstream signaling effectors for NF-κB activation. Pharmacological inhibition with ibrutinib of Bruton’s tyrosine kinase (Btk), a kinase that is required for BCR signaling to engage NF-κB, is selectively toxic for ABC DLBCL tumors; a finding that has now been translated to the clinic. These novel targets not only offer a promising new therapy options for ABC DLBCL, but also demonstrate the value of a deep molecular understanding of oncogenic signaling pathways.
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影响因子：
50.3
作者：
Chen L;Monti S;Juszczynski P;Ouyang J;Chapuy B;Neuberg D;Doench JG;Bogusz AM;Habermann TM;Dogan A;Witzig TE;Kutok JL;Rodig SJ;Golub T;Shipp MA
通讯作者：
Shipp MA
影响因子：
30.5
作者：
Dogan, Ismail;Bertocci, Barbara;Weill, Jean-Claude
通讯作者：
Weill, Jean-Claude
DOI：
10.1073/pnas.1008969108
发表时间：
2011-01-04
影响因子：
11.1
作者：
Kloo, Bernhard;Nagel, Daniel;Krappmann, Daniel
通讯作者：
Krappmann, Daniel
DOI：
10.1084/jem.20060221
发表时间：
2006-07-10
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Gazumyan A;Reichlin A;Nussenzweig MC
通讯作者：
Nussenzweig MC
DOI：
10.4049/jimmunol.0803941
发表时间：
2009-05-01
期刊：
Journal of immunology (Baltimore, Md. : 1950)
影响因子：
--
作者：
Gross AJ;Lyandres JR;Panigrahi AK;Prak ET;DeFranco AL
通讯作者：
DeFranco AL