Differential expression of survivin in bone marrow cells from patients with acute lymphocytic leukemia and chronic lymphocytic leukemia.
Survivin, a member of the inhibitor of apoptosis protein (IAP) gene family, has been detected widely in fetal tissue and in a variety of human malignancies. In the current study, we investigated the expression of IAP family proteins in bone marrow samples from acute lymphocytic leukemia (ALL), chronic lymphocytic leukemia (CLL) and control cases by quantitative real-time RT-PCR method and an immunohistochemical approach. Overexpression of survivin and cIAP2 mRNA was significant in CLL bone marrow cells (P < 0.05, respectively) compared with control samples. By immunohistochemistry, survivin was detected in a few scattered myeloid cells in all cases of control bone marrow. Concerning the ALL bone marrow, more than half the cases demonstrated positive expression of survivin (8 out of 13), while the majority of CLL cases (20 out of 21) exhibited intense expression of survivin. The differential subcellular localization of survivin was distinct between ALL and CLL cases. ALL cells essentially revealed nuclear localization of survivin as well as cytoplasmic signals in some cases, while CLL cells from the majority of cases predominantly showed cytoplasmic expression. Next, RT-PCR was performed for the expression of survivin and its splicing variant, survivin-2B and survivin-deltaEx3 in ALL and CLL cells, as the distribution of these variants would be regulated by nuclear/cytoplasmic transport system. In both ALL and CLL bone marrow samples, the expression of wild-type survivin was more predominant than that of survivin-2B or survivin-deltaEx3, although the expression of survivin-deltaEx3 was prominent in samples from survivin-expressing ALL cases. Thus, the splicing of survivin mRNA may be differently regulated in ALL and CLL cells, causing distinct manners of nuclear/cytoplasmic transport of survivin protein. In conclusion, our observations indicate a differential regulatory mechanism for the expression of IAP family proteins in ALL and CLL cells, although the functions of IAP families and the mechanisms of nuclear/cytoplasmic transport of survivin should be clarified in future studies.
Nakagawa
Yasunori
Y
Department of Pathology and Immunology, Aging and Developmental Sciences, Graduate School, Tokyo Medical and Dental University, 1-5-45 Yushima, Bunkyo-ku, Tokyo 113-8519, Japan.
Yamaguchi
Shuichi
S
Hasegawa
Maki
M
Nemoto
Tetsuo
T
Inoue
Miori
M
Suzuki
Kenshi
K
Hirokawa
Katsuiku
K
Kitagawa
Masanobu
M
D000328:Adult; D000368:Aged; D001854:Bone Marrow Cells / Q000378:metabolism*; D005260:Female; D015973:Gene Expression Regulation, Leukemic; D016158:Genes, p53; D006801:Humans; D007150:Immunohistochemistry; D051034:Inhibitor of Apoptosis Proteins; D015451:Leukemia, Lymphocytic, Chronic, B-Cell / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D008297:Male; D008869:Microtubule-Associated Proteins / Q000032:analysis / Q000235:genetics*; D008875:Middle Aged; D009154:Mutation; D009363:Neoplasm Proteins; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D012333:RNA, Messenger / Q000032:analysis; D020133:Reverse Transcriptase Polymerase Chain Reaction; D000077022:Survivin
C107489:BIRC5 protein, human; D051034:Inhibitor of Apoptosis Proteins; D008869:Microtubule-Associated Proteins; D009363:Neoplasm Proteins; D012333:RNA, Messenger; D000077022:Survivin