Objective: Survivin, a unique member of the inhibitor of apoptosis protein (IAP) family, plays an important role in regulating both apoptosis and cell division. Overexpression of survivin is associated with increased risk of recurrence and poor outcome in cancer patients. This study aimed to investigate the expression of survivin and its location as well as the relationship between cellular location and expression of survivin and the therapeutic efficacy at the cellular level.
Methods: The expression of survivin protein was detected by immunohistochemical assay in bone marrow cells from 62 children with acute leukemia and 40 hospitalized children who did not have leukemia (Control group), and in a human acute T lymphocytic leukemia cell line (Molt-4 cells) treated in vitro with daunorubicin (DNR). Cell apoptosis was detected using flow cytometry.
Results: Survivin protein was expressed in 41.9% of the 62 children with acute leukemia but in only 5.0% of the Control group (chi(2)=16.66; P < 0.01). The expression rate of survivin was 46.2% in cytoplasm and 53.9% in nucleus in the children with acute leukemia (chi(2)0.3077; P> 0.05). However, the remission rate of patients in whom survivin expression was seen in the nucleus was significantly higher than that in patients in whom survivin was expressed in cytoplasm after chemotherapy. The survivin expression in Molt-4 cells decreased remarkably by DNR treatment in a time and dosage-dependent manner. DNR treatment also induced survivin transllocation from cytoplasm to nucleus and cell apoptosis in a time and dosage-dependent manner.
Conclusions: Survivin may play an important role in the development and prognosis of childhood acute leukemia. The different expression pattern of survivin in the cytoplasm and the nucleus may be associated with therapeutic efficacy and prognosis in acute leukemia. DNR may reduce the survivin expression in leukemic cells and induce cell apoptosis.