[Expression and clinical significance of survivin in bone marrow cells of multiple myeloma patients].
OBJECTIVE
Survivin, a member of the inhibitors of apoptosis protein family (IAPs), is overexpressed in many cancers, but not in normal differentiated adult tissues. It is related to poor prognosis and resistance to chemotherapy and radiotherapy in many cancers. This study was designed to detect the expression of Survivin in bone marrow of healthy people, newly diagnosed and relapsed/refractory multiple myeloma (MM) patients, and MM cell line KM3, to explore its correlation to drug resistance and prognosis of MM patients.


METHODS
Reverse transcription-polymerase chain reaction (RT-PCR) and Western blot were used to detect mRNA and protein expression of Survivin in bone marrow samples of 17 newly diagnosed MM patients, 12 relapsed /refractory MM patients, and 9 healthy people, and myeloma cell line KM3.


RESULTS
KM3 cells expressed Survivin strongly. The positive rates and the expression levels of Survivin mRNA were significantly lower in healthy people than in newly diagnosed patients and relapsed/refractory patients (22.2 % vs. 70.5 % and 83.3 %, 0.06+/-0.04 vs. 0.31+/-0.14 and 0.69+/-0.24, P<0.01), and were significantly lower in newly diagnosed patients than in relapsed/refractory patients (P<0.05). Survivin protein were not detected in all of the healthy people; while the positive rates of Survivin were 41.4% in newly diagnosed patients and 58.3% in relapsed/refractory patients (P>0.05), and its expression levels was significantly higher in relapsed/refractory patients than in newly diagnosed patients (0.21+/-0.12 vs. 0.11+/-0.07, P<0.05). Among the 7 Survivin-positive newly diagnosed patients, 4 achieved partial remission (PR), 1 achieved MR, and 2 showed no change (NC); among the 10 Survivin-negative newly diagnosed patients, 2 achieved complete remission (CR), 4 achieved PR, 2 achieved MR, and 2 showed NC. The effective (CR+PR+MR) rate was slightly higher in Survivin-negative patients than in Survivin-positive patients (80.0% vs. 71.4%).


CONCLUSIONS
High expression of Survivin may be relates to drug resistance in some patients. Since Survivin only expressed in bone marrow cells of multiple myeloma, but not in healthy people, it can be a new target to reverse drug resistance in myeloma cells.
Li
Juan
J
Department of Hematology, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, Guangdong 510080, P. R. China. luliyuan@tom.com
Zhao
Ying
Y
Zhang
Dian-Bao
DB
Huang
Bei-Hui
BH
D000328:Adult; D000368:Aged; D000970:Antineoplastic Agents / Q000627:therapeutic use; D001854:Bone Marrow Cells / Q000378:metabolism*; D045744:Cell Line, Tumor; D019008:Drug Resistance, Neoplasm; D005260:Female; D006801:Humans; D051034:Inhibitor of Apoptosis Proteins; D008297:Male; D008869:Microtubule-Associated Proteins / Q000096:biosynthesis* / Q000235:genetics; D008875:Middle Aged; D009101:Multiple Myeloma / Q000188:drug therapy / Q000378:metabolism* / Q000473:pathology; D009363:Neoplasm Proteins / Q000096:biosynthesis* / Q000235:genetics; D009364:Neoplasm Recurrence, Local; D012333:RNA, Messenger / Q000096:biosynthesis / Q000235:genetics; D012074:Remission Induction; D000077022:Survivin
D000970:Antineoplastic Agents; C107489:BIRC5 protein, human; D051034:Inhibitor of Apoptosis Proteins; D008869:Microtubule-Associated Proteins; D009363:Neoplasm Proteins; D012333:RNA, Messenger; D000077022:Survivin