Feinberg School of Medicine, Northwestern University, Chicago, IL, United States.
Department of Periodontics, University of Illinois at Chicago, Chicago, IL, United States.
Front Immunol. 2018 Mar 12;9:481. doi: 10.3389/fimmu.2018.00481. eCollection 2018.
Neutropenic conditions are prevalent in leukemia patients and are often associated with increased susceptibility to infections. In fact, emergency granulopoiesis (EG), a process regulating neutrophil homeostasis in inflammatory conditions and infections, may occur improperly in leukemic conditions, leading to reduced neutrophil counts. Unfortunately, the mechanisms central to dysfunctional EG remain understudied in both leukemia patients and leukemic mouse models. However, despite no direct studies on EG response in leukemia are reported, recently certain transcription factors (TFs) have been found to function at the crossroads of leukemia and EG. In this review, we present an update on TFs that can potentially govern the fate of EG in leukemia. Transcriptional control of Fanconi DNA repair pathway genes is also highlighted, as well as the newly discovered role of Fanconi proteins in innate immune response and EG. Identifying the TFs regulating EG in leukemia and dissecting their underlying mechanisms may facilitate the discovery of therapeutic drugs for the treatment of neutropenia.
中性粒细胞减少症在白血病患者中很常见,并且常常与增加感染易感性有关。事实上,在炎症和感染条件下调节中性粒细胞稳态的紧急粒状细胞生成(EG),在白血病情况下可能会异常发生,导致中性粒细胞计数减少。不幸的是,白血病患者和白血病小鼠模型中,EG 功能障碍的核心机制仍未得到充分研究。然而,尽管目前没有关于白血病中 EG 反应的直接研究,但最近已经发现某些转录因子(TFs)在白血病和 EG 的交汇点发挥作用。在这篇综述中,我们介绍了可能控制白血病中 EG 命运的 TFs 的最新进展。还强调了 Fanconi DNA 修复途径基因的转录控制,以及 Fanconi 蛋白在先天免疫反应和 EG 中的新发现作用。鉴定调节白血病中 EG 的 TF 并剖析其潜在机制,可能有助于发现治疗中性粒细胞减少症的治疗药物。