Translational and Clinical Research Institute, Newcastle University, Newcastle upon Tyne NE1 7RU, UK.
Maria Skłodowska-Curie Institute, Oncology Center, Gliwice Branch, 02-034 Gliwice, Poland.
Int J Mol Sci. 2020 Oct 16;21(20):7663. doi: 10.3390/ijms21207663.
Chronic lymphocytic leukemia (CLL) is the most common adult leukemia in the Western World and it is characterized by a marked degree of clinical heterogeneity. An impaired balance between pro- and anti-apoptotic stimuli determines chemorefractoriness and outcome. The low proliferation rate of CLL cells indicates that one of the primary mechanisms involved in disease development may be an apoptotic failure. Here, we study the clinical and functional significance of DRAK2, a novel stress response kinase that plays a critical role in apoptosis, T-cell biology, and B-cell activation in CLL. We have analyzed CLL patient samples and showed that low expression levels of DRAK2 were significantly associated with unfavorable outcome in our CLL cohort. expression levels showed a positive correlation with the expression of , and . Consistent with clinical data, the downregulation of DRAK2 in MEC-1 CLL cells strongly increased cell viability and proliferation. Further, our transcriptome data from MEC-1 cells highlighted MAPK, NF-κB, and Akt and as critical signaling hubs upon knockdown. Taken together, our results indicate DRAK2 as a novel marker of CLL survival that plays key regulatory roles in CLL prognosis.
慢性淋巴细胞白血病（CLL）是西方世界最常见的成人白血病，其特征是明显的临床异质性。促凋亡和抗凋亡刺激之间的平衡失调决定了化疗耐药性和预后。CLL 细胞的低增殖率表明，疾病发展中涉及的主要机制之一可能是凋亡失败。在这里，我们研究了 DRAK2 的临床和功能意义，DRAK2 是一种新型应激反应激酶，在凋亡、T 细胞生物学和 CLL 中的 B 细胞激活中发挥关键作用。我们已经分析了 CLL 患者样本，并表明 DRAK2 的低表达水平与我们的 CLL 队列中的不良预后显著相关。 表达水平与 、 和 的表达呈正相关。与临床数据一致，在 MEC-1 CLL 细胞中下调 DRAK2 会强烈增加细胞活力和增殖。此外，我们从 MEC-1 细胞获得的转录组数据突出了 MAPK、NF-κB 和 Akt 作为 敲低后关键信号枢纽。总之，我们的结果表明 DRAK2 是 CLL 生存的一个新标志物，它在 CLL 预后中发挥关键调节作用。
