Expression Of Survivin, Bcl-2, Mdr1 In Childhood Acute Leukemia And Its Clinical Significance

Objective: Acute leukemia (AL) is the most common malignant tumor in children. In recent twenty years, the 5-year disease-free survival has reached about 70% in acute lymphocytic leukemia (ALL) in children by chemotherapy and hematopoietic stem cell transplantation. However, its pathogenesis is still no clear. Deregulation of apoptosis has been implicated in carcinogenesis by abnormally prolonged cell survival, facilitating the accumulation of transforming mutations, and promoting resistance to immunosurveillance. Moreover, impairment of apoptotic cell death might significantly affect resistance of cancer cells to chemotherapy and irradiation. Survivin, a novel apoptosis inhibitor of the IAP gene family, was recently found in all of the most common human cancers but not in normal and terminally differentiated adult tissues. Survivin was found in adult acute leukemia with high level. It is suggested that the high level expression of survivin in adult acute leukemia patients may be related with the poor prognosis and drug resistance. However the expression of survivin in pediatric patients with acute leukemia is seldom reported. So, the objective of this project is to study the expression of survivin in childhood AL and the relationship of the expression of survivin, bcl-2 , mdr1 and the clinical manifestation. Methods: Fifty-three children with AL were enrolled in this study. Four groups were set up, which includes newly diagnosed group, complete remission (CR) group, relapse group, and the control group including 15 children's patients without malignance disease. The expression of survivin, bcl-2 and mdr1 in all patients were examined by RT-PCR. Results: The positive expression of surviving, bcl-2 and mdr1 is 26 (60.47%), 26 (60.47%), and 15 (34.88%) respectively in the newly diagnosed AL group (N=43), which is higher than that in the control group (P<0.05). There is no significant difference of the expression of survivin, bcl-2 and mdr1 between ALL and AML group (P>0.05). The positive expression of survivin and bcl-2 in the CR group is significantly lower than that in the newly diagnosed AL group (P<0.05). The positive expression of mdr1 in the CR group is lower than that in the newly diagnosed AL group, but there is no significant difference between the two groups (P>0.05). 16 (37.21%) patients in the newly diagnosed AL group had survivin and bcl-2 both positive. The positive expression of survivin in the patients with positive bcl-2 and negative bcl-2 is 16 (61.54%, N=26) and 10 (58.82%, N=17) respectively. There is no significant difference between the two groups (P>0.05). 10 patients had survivin and mdr1 both positive. The positive expression of survivin in the patients with positive mdr1 and negative mdr1 is 10 (66.67%,N=15) and 16(57.14%,N=28) respectively. There is no significant difference between this two groups (P>0.05). All survivin, bcl-2 and mdr1 positive were found in 3 patients of the newly diagnosed AL group, 2 patients of the relapse group, but no patients in the CR group. The WBC is 37.20×109/L±69.90×109/L and 51.86×109/L±95.47×109/L in the patients with positive survivin and negative survivin respectively. There is no significant difference between these two groups (P>0.05).Conclusions: The newly diagnosed childhood AL patients had higher expression of survivin and bcl-2, which may contribute to the pathogenesis and the progress of the leukemia. The relationship of the expression of survivin and bcl-2 with the type of leukemia and the WBC in the peripheral blood was not found in this study. Also, there is no relationship was found among the expression of survivin, bcl-2 and mdr1. The positive expression of survivin and bcl-2 decreased with the disease remission. The positive expression of all three marker of survivin, bcl-2 and mdr1 predicted relapse or poor prognosis, which suggested that survivin and bcl-2 may become a marker for the treatment evaluation for the childhood AL patients.