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.