Predictive values of plasma TNFα and IL-8 for intracranial hemorrhage in patients with acute promyelocytic leukemia

Abstract

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 α 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.

Keywords

acute promyelocytic leukemia / intracranial hemorrhage / cytokines / biomarker

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Acknowledgements

This work was supported by the National Natural Science Foundation of China (Nos. 81890994, 81770144, 81870119, 81800141, and 81770153) and the National Key Research and Development Program (No. 2019YFA0905900).

Compliance with ethics guidelines

Fangyi Dong, Li Chen, Chaoxian Zhao, Xiaoyang Li, Yun Tan, Huan Song, Wen Jin, Hongming Zhu, Yunxiang Zhang, Kai Xue, Junmin Li, and Kankan Wang declare that they have no conflict of interest. All procedures followed were in accordance with the ethical standards of the responsible committee on human experimentation (institutional and national) and with the Helsinki Declaration of 1975, as revised in 2000 (5). Informed consent was obtained from all patients for being included in the study. All institutional and national guidelines for the care and use of laboratory animals were followed.

Electronic Supplementary Material

Supplementary material is available in the online version of this article at https://doi.org/10.1007/s11684-021-0890-1 and is accessible for authorized users.

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