B cell receptor signaling in chronic lymphocytic leukemia.

B cell receptor signaling in chronic lymphocytic leukemia.
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DOI:
10.1016/j.it.2013.07.002
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发表时间:
2013-12
影响因子:
16.8
通讯作者:
Chiorazzi N
Chiorazzi N
中科院分区:
医学1区
文献类型:
--
作者:
Burger JA;Chiorazzi N

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基于BCR的结构限制以及恶性B细胞的BCR依赖性存活和生长,BCR信号传导在慢性淋巴细胞白血病(CLL)和B细胞淋巴瘤中起重要的致病作用。在CLL和淋巴瘤亚型中,配体非依赖性(“补品”)和配体依赖性BCR信号传导已被表征,这可能涉及BCR途径组分的突变或由组织微环境中存在的(自身)抗原触发。在CLL中,基于早期临床试验中的高缓解率和持久缓解,靶向BCR相关激酶(BTK,PI3 K δ)的抑制剂正在快速临床开发,这将改变CLL和其他B细胞恶性肿瘤的治疗模式。在这里,我们讨论了这一领域的发展,从BCR相关的预后标志物,BCR激活的机制,靶向BCR相关激酶,新出现的致命弱点在CLL发病机制。
BCR signaling plays an important pathogenic role in chronic lymphocytic leukemia (CLL) and B cell lymphomas, based on structural restrictions of the BCR, and BCR-dependent survival and growth of the malignant B cells. In CLL and lymphoma subtypes, ligand-independent (“tonic”) and ligand-dependent BCR signaling have been characterized, which can involve mutations of BCR pathway components or be triggered by (auto-) antigens present in the tissue microenvironment. In CLL, based on high response rates and durable remissions in early-stage clinical trials, there is rapid clinical development of inhibitors targeting BCR-associated kinases (BTK, PI3Kδ), which will change treatment paradigms in CLL and other B cell malignancies. Here, we discuss the evolution of this field, from BCR-related prognostic markers, to mechanisms of BCR activation, and targeting of BCR-associated kinases, the emerging Achilles’ heel in CLL pathogenesis.
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