Purpose: Acute myeloid leukemia (AML) is associated with a poor overall prognosis. PIM family genes, including PIM1, PIM2 , and PIM3 , are proto-oncogenes that are aberrantly overexpressed in different types of human cancers. In this study, we aimed to explore and clarify the function of PIM3  in AML.
Patients and Methods: The expression of the three PIM  genes in AML was detected using the Gene Expression Omnibus. The expression of PIM3  and PIM3 in patient samples and AML cell lines was measured using quantitative real-time polymerase chain reaction or Western blot analyses. The cellular behaviors of PIM3 -overexpressing AML cell lines were detected using a CCK-8 assay, flow cytometry, Western blotting, immunofluorescence staining, and a cell migration assay. The interactions between PIM3 and phosphorylated CXCR4 (pCXCR4) were explored via immunoprecipitation.
Results: Higher PIM3  expression was detected in primary AML cells than in healthy donor cells. Second, PIM3  overexpression promoted AML cell proliferation and protected against spontaneous apoptosis by phosphorylating BAD (pBAD) at Ser112. Furthermore, PIM3  overexpression might promote the migration of AML cells via CXCR4. PIM3 -overexpressing AML cell lines exhibited increased CXCR4 phosphorylation at Ser339, and pCXCR4 interacted with PIM3.
Conclusion: Our findings suggest that PIM3 regulates the proliferation, survival, and chemotaxis of AML cell lines. Moreover, pCXCR4 might mediate the regulation of PIM3-induced chemotaxis. Therefore, the inhibition of PIM3  expression may be a promising therapeutic target in AML.
Keywords: pBAD, pCXCR4, PIM1 , PIM2 , PIM3