Li Boheng, Wan Qin, Li Zhubo, Chng Wee-Joo
College of Pharmaceutical Sciences, Southwest University, Chongqing 400715, China.
Department of Haematology-Oncology, National University Cancer Institute of Singapore, Singapore 119074, Singapore.
Cancers (Basel). 2021 Oct 14;13(20):5147. doi: 10.3390/cancers13205147.
The Janus kinase (JAK) family are known to respond to extracellular cytokine stimuli and to phosphorylate and activate signal transducers and activators of transcription (STAT), thereby modulating gene expression profiles. Recent studies have highlighted JAK abnormality in inducing over-activation of the JAK/STAT pathway, and that the cytoplasmic JAK tyrosine kinases may also have a nuclear role. A couple of anti-JAK therapeutics have been developed, which effectively harness lymphoid cancer cells. Here we discuss mutations and fusions leading to JAK deregulations, how upstream nodes drive JAK expression, how classical JAK/STAT pathways are represented in lymphoid malignancies and the noncanonical and nuclear role of JAKs. We also summarize JAK inhibition therapeutics applied alone or synergized with other drugs in treating lymphoid malignancies.
已知Janus激酶（JAK）家族可响应细胞外细胞因子刺激，使信号转导子和转录激活子（STAT）磷酸化并激活，从而调节基因表达谱。最近的研究强调了JAK异常可诱导JAK/STAT途径过度激活，并且细胞质JAK酪氨酸激酶可能也具有核功能。已经开发了几种抗JAK疗法，它们可有效控制淋巴瘤细胞。在此，我们讨论导致JAK失调的突变和融合、上游节点如何驱动JAK表达、经典JAK/STAT途径如何在淋巴瘤中表现以及JAK的非经典和核功能。我们还总结了单独应用或与其他药物联合应用于治疗淋巴瘤的JAK抑制疗法。
