Purpose: To elucidate the role of AKAP12 in leukemia cells.Methods: Quantitative reverse transcription-polymerase chain reaction (qRT-PCR) and Western blotting (WB) were employed to determine the expression of AKAP12 in leukocyte cell lines, while 5-azacytidine was used to treat the cells, followed by assessment of the expression of AKAP12. After constructing the overexpressing vector pc-AKAP12 and transfecting it into cells or treating the cells with 5-azacytidine, cell counting kit-8 assay (CCK-8) was used to determine cell proliferation. Cloning ability of the cells was evaluated by colony formation assay.  Furthermore, flow cytometry was employed to measure the degrees of cell cycle and cell apoptosis. The effect of AKAP12 on PI3K/AKT were determined by western blot.Results: The results showed that AKAP12 was lowly expressed in lymphocytic leukemia cell lines (p < 0.001), but was reversed by 5-azacytidine. Transfection of AKAP12 or 5-azacytidine treatment increased the expression of AKAP12 in the cells (p > 0.001), inhibited leukemia cell proliferation and clonality, and arrested cell cycle in G1 phase as well as induced apoptosis. In addition, PI3K/AKT signaling pathway was inhibited by AKAP12.Conclusion: AKAP12 is lowly expressed in leukemia cells, and may also play a role in inhibiting leukemia progression by suppressing the activity of PI3K/AKT pathway.Thus, targeting AKAP12 mght be a potential strategy in the management of lukemia.