The B cell receptor (BCR) is a master regulator of B cells, controlling cellular processes such as proliferation, migration and survival. Cell signalling downstream of the BCR is aberrantly activated in the B cell malignancy chronic lymphocytic leukaemia (CLL), supporting the pathophysiology of the disease. This insight has led to development and approval of small molecule inhibitors that target components of the BCR pathway. These advances have greatly improved the management of CLL, but the disease remains incurable. This may partly be explained by the inter‐patient heterogeneity of the disease, also when it comes to treatment responses. Precision medicine is therefore required to optimize treatment and move towards a cure. Here, we discuss how the introduction of BCR signalling inhibitors has facilitated the development of functional in vitro assays to guide clinical treatment decisions on use of the same therapeutic agents in individual patients. The cellular responses to these agents can be analysed in high‐throughput assays such as dynamic BH3 profiling, phospho flow experiments and drug sensitivity screens to identify predictive biomarkers. This progress exemplifies the positive synergy between basal and translational research needed to optimize patient care.

中文翻译：

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B细胞信号通路-CLL中精准医学的新目标。

B细胞受体（BCR）是B细胞的主要调节剂，可控制细胞进程，例如增殖，迁移和存活。BCR下游的细胞信号在B细胞恶性慢性淋巴细胞性白血病（CLL）中异常激活，从而支持了该疾病的病理生理。这种见解导致开发和批准了靶向BCR途径组分的小分子抑制剂。这些进展极大地改善了CLL的治疗，但该疾病仍然无法治愈。这可能部分是由于疾病的患者间异质性，也涉及到治疗反应。因此，需要精密药物来优化治疗并走向治愈。这里，我们讨论了BCR信号抑制剂的引入如何促进功能性体外测定的发展，以指导在个别患者中使用相同治疗剂的临床治疗决策。可以在高通量分析中分析对这些药物的细胞反应，例如动态BH3分析，磷流实验和药物敏感性筛选，以鉴定预测性生物标志物。这一进展例证了优化患者护理所需的基础研究和转化研究之间的积极协同作用。