[Expression of survivin and its location in bone marrow cells of childhood acute leukemia: relationship to therapeutic efficacy].
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.
Hou
Yan
Y
Research Laboratory of Pediatric Hematology, Tongji Hosipital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China.
Hu
Qun
Q
Liu
Ai-Guo
AG
Zhang
Liu-Qing
LQ
Liu
Shuang-You
SY
D000293:Adolescent; D017209:Apoptosis / Q000187:drug effects; D001854:Bone Marrow Cells / Q000737:chemistry*; D002648:Child; D002675:Child, Preschool; D003630:Daunorubicin / Q000494:pharmacology / Q000627:therapeutic use*; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D007223:Infant; D051034:Inhibitor of Apoptosis Proteins; D015470:Leukemia, Myeloid, Acute / Q000188:drug therapy / Q000378:metabolism* / Q000473:pathology; D008297:Male; D008869:Microtubule-Associated Proteins / Q000032:analysis*; D009363:Neoplasm Proteins / Q000032:analysis*; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000188:drug therapy / Q000378:metabolism* / Q000473:pathology; D000077022:Survivin
C107489:BIRC5 protein, human; D051034:Inhibitor of Apoptosis Proteins; D008869:Microtubule-Associated Proteins; D009363:Neoplasm Proteins; D000077022:Survivin; D003630:Daunorubicin