Shanghai Institute of Hematology, State Key Laboratory of Medical Genomics, National Research Center for Translational Medicine at Shanghai, Ruijin Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, 20025, China.
CNRS-LIA Hematology and Cancer, Sino-French Research Center for Life Sciences and Genomics, Ruijin Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, 200025, China.
Front Med. 2022 Dec;16(6):909-918. doi: 10.1007/s11684-021-0890-1. Epub 2022 Sep 12.
In patients with acute promyelocytic leukemia (APL), intracranial hemorrhage (ICH), if not identified promptly, could be fatal. It is the leading cause of failure of induction and early death. Thus, biomarkers that could promptly predict severe complications are critical. Here, cytokine differences between patients with APL with and without ICH were investigated to develop predictive models for this complication. The initial cytokine profiling using plasma samples from 39 patients and 18 healthy donors found a series of cytokines that were remarkedly different between patients with APL and healthy controls. The APL patients were subsequently divided into high and low white blood cell count groups. Results showed that tumor necrosis factor a and interleukin 8 (IL-8) were vital in distinguishing patients with APL who did or did not develop ICH. In addition, verification in 81 patients with APL demonstrated that the two cytokines were positively correlated with the cumulative incidence of ICH. Finally, in-vitro and in-vivo experimental evidence were provided to show that IL-8 influenced the migration of APL-derived NB4 cells and impaired the blood-brain barrier in PML/RARα positive blast-transplanted FVB/NJ mice. These assessments may facilitate the early warning of ICH and reduce future mortality levels in APL.
在急性早幼粒细胞白血病 (APL) 患者中，如果不能及时发现颅内出血 (ICH)，可能会致命。ICH 是诱导失败和早期死亡的主要原因。因此，能够及时预测严重并发症的生物标志物至关重要。在这里，研究了 APL 患者与 ICH 患者之间的细胞因子差异，以开发该并发症的预测模型。使用来自 39 名患者和 18 名健康供体的血浆样本进行的初始细胞因子分析发现了一系列在 APL 患者和健康对照者之间明显不同的细胞因子。随后将 APL 患者分为白细胞计数高和低的两组。结果表明，肿瘤坏死因子 a 和白细胞介素 8 (IL-8) 在区分是否发生 ICH 的 APL 患者方面非常重要。此外，在 81 名 APL 患者中的验证表明，这两种细胞因子与 ICH 累积发生率呈正相关。最后，提供了体外和体内实验证据，表明 IL-8 影响 APL 衍生的 NB4 细胞的迁移，并损害 PML/RARα 阳性白血病细胞移植 FVB/NJ 小鼠的血脑屏障。这些评估可能有助于及早预警 ICH 并降低 APL 的未来死亡率。
