CXCL12, a chemokine abundantly produced by the bone marrow microenvironment, and its receptor CXCR4 have crucial roles in malignant cell trafficking.In the present study CXCR4 expression was investigated by flowcytometry and CXCL12 G801A gene polymorphism was detected by PCR-RFLP assay in 42 patients with de novo AML as well as 35 normal subjects as a control group. The CXCR4 positive expression was found exclusively in AML patients and not in the control subjects. The incidence of positive CXCR4 receptor expression was in 54.8% of AML patients. The frequency of the CXCL12 genotypes among AML patient were: 54.8 % had a (GG) alleles genotype while 45.2 % had an (A) allele genotype (38.1 % were A/G & 7.1 % were A/A) while among the control group 82.9% had a (GG) alleles genotype and 17.1% had an (A) allele genotype (All were A/G). The CXCL12 A allele (A/G & A/A) genotype was significantly associated with extramedullary tissue infiltration which was found in 66.7% of CXCL12 A allele (A/G & A/A) genotype AML patients. There was a statistically significant relationship between the CXCL12 genotypes and CXCR4 expression and outcome of treatment. In CXCL12 A allele carrier (A/G & A/A) genotypes AML patients; 13.3% had favorable prognosis and 63% had unfavorable prognosis.In CXCR4 positive group 26.7% of patients had favorable prognosis and 70.4% had unfavorable prognosis .In conclusion CXCR4 expression predicts poor prognosis in AML and CXCL12 G801A polymorphism is a genetic determinant involved in the clinical presentation of leukemia.