Background: Acute myeloid leukemia (AML) is a complex and heterogeneous hematopoietic tissue neoplasm caused by gene mutations, chromosomal rearrangement and deregulation of gene expression. Inositol polyphosphate 4-phosphatase type II (INPP4B) is a clinically relevant factor in the phosphoinositide 3 kinase (PI3K) pathway- associated cancers, has been found to have a bad prognostic role in AML. However, the exact mechanism is still unclear. Objective: We aimed in this study to investigate the prognostic role of INPP4B overexpression in Egyptian AML patients. Patients and methods: A total of 80 patients with newly diagnosed AML were included in the study. In addition, 40 apparently healthy, age and sex matched subjects served as control group. Immunophenotyping, cytogenetic analysis and quantitative assessment of INPP4B gene transcript were performed using real time PCR. Results: INPP4B overexpression was detected in 27.5 % of newly diagnosed AML patients. There was a statistically significant decrease in the probability of achieving complete remission (CR) with shorter overall survival (OS), event free survival (EFS) and disease-free survival (DFS) in the INPP4B high expression group compared with the low expression group (p=0.003, 0.03, 0.02 and <0.001; respectively). Conclusion: We can conclude thatINPP4B overexpression is associated with poor response to therapy with poor outcome, and add prognostic value in patients with AML. INPP4B overexpression could be a valuable tool for making therapeutic decisions.