Department of Hematology, the First Affi liated Hospital of Nanjing Medical University, Jiangsu Province Hospital, Nanjing, China.
Leuk Lymphoma. 2013 Jun;54(6):1165-70. doi: 10.3109/10428194.2012.736983. Epub 2012 Nov 2.
There is now strong evidence that B-cell receptor (BCR) signaling plays a major role in the development of chronic lymphocytic leukemia (CLL). The purpose of this study was to investigate the expression levels of some of the molecules involved in the signaling cascade originating from the BCR (Syk, Lyn, PLCγ2, ERK) and analyze possible correlations of mRNA levels with biological/clinical features. Our study population consisted of 92 consecutive patients with newly diagnosed CLL. Several genes of BCR signaling (Lyn, Syk, PLCγ2 and ERK) and ZAP-70 were measured by quantitative polymerase chain reaction (qPCR). The signaling molecules of BCR were strongly associated with each other, and ZAP-70 correlated well with Lyn, Syk, PLCγ2 and ERK. Associations between treatment response and Lyn, Syk, PLCγ2 and ERK were not found. Moreover, a higher level of Lyn mRNA was associated with a shorter treatment-free survival (TFS) (univariate analysis only; multivariate Cox analysis showed that only ZAP-70 and Binet stage were independent prognostic factors and associated with TFS). Though Lyn was not an independent prognostic factor, it still might be a new therapy target of CLL. BCR signaling provides perspectives for future development of an exciting new class of kinase inhibitors.
目前有强有力的证据表明，B 细胞受体（BCR）信号在慢性淋巴细胞白血病（CLL）的发展中起着主要作用。本研究旨在调查源自 BCR 的信号级联中一些参与分子的表达水平（Syk、Lyn、PLCγ2、ERK），并分析 mRNA 水平与生物学/临床特征的可能相关性。我们的研究人群由 92 例新诊断的 CLL 连续患者组成。通过定量聚合酶链反应（qPCR）测量 BCR 信号（Lyn、Syk、PLCγ2 和 ERK）和 ZAP-70 的几个基因。BCR 的信号分子彼此之间具有很强的相关性，并且 ZAP-70 与 Lyn、Syk、PLCγ2 和 ERK 很好地相关。未发现治疗反应与 Lyn、Syk、PLCγ2 和 ERK 之间存在关联。此外，较高水平的 Lyn mRNA 与无治疗生存时间（TFS）较短相关（仅单变量分析；多变量 Cox 分析表明，只有 ZAP-70 和 Binet 分期是独立的预后因素，并与 TFS 相关）。尽管 Lyn 不是独立的预后因素，但它可能仍然是 CLL 的一个新的治疗靶点。BCR 信号为未来开发一类令人兴奋的新型激酶抑制剂提供了前景。
