Synergistic role of JAK/STAT5 and PI3K/AKT signaling pathways in regulating eIF4B in acute leukemia.

Yun MA; Tingting LI; Riyue Feng; Guijie Guo; Qidong Pan; Jianning LI; Jilong Chen

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Synergistic role of JAK/STAT5 and PI3K/AKT signaling pathways in regulating eIF4B in acute leukemia.

Author: Yun MA ¹ ; Tingting LI ² ; Riyue FENG ¹ ; Guijie GUO ¹ ; Qidong PAN ² ; Jianning LI ¹ ; Jilong CHEN ¹
Author Information

1. Key Laboratory of Pathogenic Microbiology and Immunology, Institute of Microbiology, Chinese Academy of Sciences, Beijing 100101, China.
2. College of Animal Sciences, Fujian Agriculture and Forestry University, Fuzhou 350002, Fujian, China.
Publication Type:Journal Article
Keywords: JAK/STAT5/Pim; PI3K/AKT/mTOR; acute leukemia; eIF4B
MeSH: Animals; Apoptosis; Cell Line, Tumor; Leukemia; Mice; Mice, Nude; Phosphatidylinositol 3-Kinases/metabolism*; Proto-Oncogene Proteins c-akt/metabolism*; STAT5 Transcription Factor/metabolism*
From: Chinese Journal of Biotechnology 2020;36(11):2413-2423
CountryChina
Language:Chinese
Abstract: Human acute leukemia (AL) is a clonal malignancy with abnormal hematopoietic stem cells. Clinically, AL is very difficult to cure due to its sudden onset and short course of disease progression. Previous studies have shown that eukaryotic initiation factor 4B (eIF4B) plays a critical role in the development of chronic leukemia. However, the involvement of eIF4B in human acute leukemia is still largely unknown. Therefore, we studied eIF4B function and its regulatory mechanism in human acute leukemia. We found that phosphorylation levels of eIF4B in acute leukemia cells were significantly reduced in response to treatment with either LY294002 (PI3K inhibitor), AKTi (AKT inhibitor) or SMI-4A (Pim inhibitor). Co-treatment with inhibitors targeting JAK/STAT5/Pim and PI3K/AKT/mTOR signaling dramatically promoted apoptosis of acute leukemia cells by downregulating eIF4B phosphorylation. Furthermore, in vitro and in vivo functional experiments showed that eIF4B played an important anti-apoptosis role in the acute leukemia cells by regulating the expression of anti-apoptotic proteins Bcl-2 and Bcl-XL. In contrast, silencing eIF4B inhibited the growth of acute leukemia cells as engrafted tumors in nude mice. Taken together, our results indicate the synergistic role of JAK/STAT5/Pim and PI3K/AKT/mTOR signaling pathways in regulating eIF4B phosphorylation in acute leukemia, and highlight eIF4B as a candidate therapeutic target for treatment of acute leukemia.