Clinical outcomes in chronic lymphocytic leukaemia associated with expression of CD5, a negative regulator of B-cell receptor signalling.
Clinical outcomes in chronic lymphocytic leukaemia associated with expression of CD5, a negative regulator of B-cell receptor signalling.
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DOI：
10.1111/bjh.15632
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发表时间：
2018-12
影响因子：
6.5
通讯作者：
Weinberg JB
中科院分区：
文献类型：
--
作者：
Friedman DR;Guadalupe E;Volkheimer A;Moore JO;Weinberg JB
慢性淋巴细胞白血病（CLL）的特征在于克隆B细胞上的CD 5表达，并且部分由活化的B细胞受体（BCR）信号传导驱动。虽然已知CD5是BCR信号传导的负调节因子，但尚不清楚患者中是否存在CD5表达的变异性以及CLL细胞CD5表达是否影响CLL临床结局。我们评估了CD5表达与临床结果相关的程度，以及这些信息是否增加了目前使用的预后标志物。我们评估了来自杜克大学和达勒姆弗吉尼亚州医学中心的1275例血液样本的CD5表达，建立了预后标志物和423例CLL患者的事件发生时间数据。CD5中位荧光强度（MFI）在ss个体患者中随时间推移基本稳定，但在整个队列中范围在0.5至760之间。较低的CD5 MFI与较短的首次治疗时间显著相关。CD5 MFI与已建立的临床和分子预后标志物相结合，显著改善了风险分层。CD5可能通过抑制BCR信号传导影响疾病结局。因此，调节CLL细胞CD5表达或功能的策略可能是CLL的治疗方法。
Chronic lymphocytic leukaemia (CLL) is characterized by expression of CD5 on clonal B cells, and is partly driven by activated B-cell receptor (BCR) signalling. While CD5 is known to be a negative regulator of BCR signalling, it is unknown if variability in CD5 expression exists among patients and whether CLL cell CD5 expression affects CLL clinical outcomes. We assessed the extent to which CD5 expression is correlated with clinical outcomes, and whether this information adds to currently used prognostic markers. We evaluated CD5 expression from 1275 blood samples, established prognostic markers and time to event data from 423 CLL patients followed at the Duke University and Durham VA Medical Centers. CD5 median fluorescence intensity (MFI) was largely stable over time in ssindividual patients, but ranged between 0.5 and 760 in the entire cohort. Lower CD5 MFI was significantly associated with a shorter time to first therapy. CD5 MFI, combined with established clinical and molecular prognostic markers, significantly improved risk-stratification. CD5 may affect disease outcomes by suppressing signalling through the BCR. Thus, a strategy to modulate CLL cell CD5 expression or function could be a therapeutic approach in CLL.
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DOI：
10.1016/j.bbamcr.2015.07.009
发表时间：
2016-03
期刊：
Biochimica et biophysica acta
影响因子：
--
作者：
Ten Hacken E;Burger JA
通讯作者：
Burger JA
影响因子：
4.8
作者：
Gary-Gouy, H;Bruhns, P;Bismuth, G
通讯作者：
Bismuth, G
影响因子：
12.8
作者：
Friedman, Daphne R.;Sibley, Alexander B.;Wilcox, Ryan A.
通讯作者：
Wilcox, Ryan A.
影响因子：
3.1
作者：
Demir, Cengiz;Kara, Erdal;Ebinc, Senar
通讯作者：
Ebinc, Senar
影响因子：
20.3
作者：
Herman, Sarah E. M.;Gordon, Amber L.;Byrd, John C.
通讯作者：
Byrd, John C.