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The angiogenic-related factors, angiopoietin-1 and angiopoietin-2 and their receptor Tie-2, have wide-ranging effects on tumor behavior that includes angiogenesis and inflammation. These multifaceted pathways present a potential target in developing novel inhibition strategies for cancer therapy. The present work aimed at detecting the prevalence of expression of angiopoietin-1, angiopoietin-2, and their receptor Tie-2 in 56 Egyptian de novo acute myeloid leukemia (AML) patients by conventional RT-PCR to verify the prognostic impact of their expression on the response to induction chemotherapy. Thirty age- and sex-matched healthy volunteers were subjected to the same analysis as a control group. High expression of Ang-1 was detected in the patient group but not the control group. AML patients expressing Ang-2 either solely or in combination with high Ang-1 and/or Tie-2 showed unfavorable response to induction chemotherapy, either failed induction or death during induction. These data provide evidence that the alternation of angiopoietin balance in favor of Ang-2 may play a critical role in the pathophysiology of AML. Furthermore, positive pre-therapeutic expression of Ang-2 indicates viable unfavorable prognostic marker in AML patients and may be used as a prognostic tool in the risk-adaptive management of AML.