Expression of heparanase gene in Egyptian acute leukemia patient

ABSTRACT

Heparanase is an endoglycosidase that degrades heparin sulfate, the main polysaccharide constituent of the extracellular matrix and basement membrane. Expression of the heparanase gene is associated with the invasive, angiogenic, and metastatic potential of diverse malignant tumors and cell lines. to investigate possible relation/correlation between Heparanase gene expression and quantitation in pediatric Acute leukemia patients and clinicopathologic variables as well as patients outcome in an attempt to determine it's prognostic value and the possibility of using it as a new target for treatment. Forty pediatric acute leukemia patients [20 acute myeloid leukemia [AML] and 20 acute lymphoblastic leukemia [ALL] as well as 11 normal volunteers were analyzed for the expression and level of Heparanase gene using real time quantitative reverse transcriptase polymerase chain reaction [RTQ-PCR] to investigate a possible relation, association, or correlation with the clinical and laboratory features of patients at diagnosis, and patient outcome after treatment and follow up. Comparing the 3 groups as regards the Heparanase gene level there was high statistical significant difference [p<0.001] being maximum in AML and minimum in controls, with mean Relative quantitation [RQ] level 2336.2 +/- 10405.2 in AML ,median 8.0 and range [3.1-46543.0], while mean RQ in ALL was 1.7 +/- 1.0 ,median 1.7 and range [0.1-3.1] and in controls mean was 0.8+/-0.3, median 0.8 and range [0.4-1.4].Comparison between each 2 groups as regards heparanase level was of high statistically significant difference, p value being [p<0.001] when comparing AML/ALL and AML/controls and [p=0.035] when comparing ALL/controls. Cut off value for heparanase gene was calculated using Roc curve and was found to be 1.413 with 80% sensitivity and 100% specificity. According to this cut off level, 20/20 [100%] AML cases were heparanase positive, 12/20 [60%] [[ALL] cases were heparanase positive and 8/20 ALL patients were negative, while all controls [100%] were negative. This was of high statistical significance [p<0.001]. Comparing the overall survival [OS] of AML/ALL there was no statistically significant difference [p=0.2916], while comparing the disease free survival [DPS] of AML/ALL was of statistical significant difference [0.0312]. Comparing the final status of the disease [complete remission [CR]/ progressive disease [PD] or death] as regards the heparanase gene level RQ, showed a high statistical significant difference [p<0.005] with the level being higher in patients with PD/death. There was no significant correlation between all group and heparanase gene level as regards age, TLC, hemoglobin, platelets and peripheral blood blasts [p=0.353,0.704,0.844,0.54 and 0.097] respectively, while there was significant negative correlation on comparing bone marrow blast% and heparanase gene level [r=-0.408 and p=0.09]. Heparanse gene is expressed in acute leukemia being higher in AML than ALL and controls. Patients with higher heparanase gene showed poorer outcome. These findings suggest that heparanase gene may be a novel significant therapeutic target for acute leukemia