Elevated nuclear phospho-eIF4E body levels are associated with tumor progression and poor prognosis for acute myeloid leukemia

Uncontrolled proliferation is a hallmark of cancer cells, yet the molecular mechanisms that contribute to this proliferation are unclear. Therapeutic treatment of cancer is suboptimal in many cases, with no accurate index by which to evaluate the success of treatment or patient prognosis. In this study, we explored the protein levels of nuclear phospho-eIF4E in acute myeloid leukemia (AML) cell lines and primary leukemia samples by Western blot and immunofluorescence and as well analyzed transcriptomes by RNA-seq. We found nuclear phospho-eIF4E, an exporter of oncogenic mRNAs, to be abundant in AML. Further, nuclear phospho-eIF4E abundance was significantly associated with tumor burden as well as the response of AML patients to chemotherapy. The results demonstrate massive clustering and export of oncogenic mRNAs to the translation machinery by highly abundant RNA-nuclear phospho-eIF4E bodies. This is an efficient mechanism that may drive the proliferation of cancer cells. Herein, nuclear phospho-eIF4E bodies were identified as potential markers of AML, which may be useful for prognosis and as targets for cancer therapy.

Automated summary

In this study, nuclear phospho-eIF4E was found to be abundant in AML and significantly associated with tumor burden and patient response to chemotherapy. The massive clustering and export of oncogenic mRNAs by nuclear phospho-eIF4E bodies may efficiently drive cancer cell proliferation. These findings suggest that nuclear phospho-eIF4E bodies could serve as potential markers for AML prognosis and targets for cancer therapy.