Expression of DNA repair gene Ku80 in lymphoid neoplasm.
OBJECTIVE
Ku, a heterodimer of KU70 and Ku80 that binds to double-strand DNA breaks (DSBs) and activates the catalytic subunit (DNA-PKcs) when DNA is bound, is essential in DSB repair and V(D)J recombination. Ku80 is a putative tumor suppressor gene that might play an important role in drug resistance. Our aim was to determine the role of Ku80 in lymphoid malignancy.


METHODS
Competitive reverse transcription-polymerase chain reaction assays were performed and the expression levels of Ku80 were measured in normal peripheral blood mononuclear cells (n = 9) and malignant cells from 25 patients with acute lymphoblastic leukemia (ALL) (14 children, 11 adults), and chronic lymphoproliferative disorders (n = 6). The Ku80 transcripts were sequencing for the possibility of mutation.


RESULTS
No mutation or Ku80 variant at the RNA level was seen in any patient samples or in the Raji or CCRF-CEM cell lines. In Ku80 expression, 8.8-, 1.9-, and 6.2-fold mean increases were seen in adult, pediatric ALL, and chronic lymphoid malignancies compared with the control. The Ku80 was significantly higher in adult than in pediatric ALL (P = 0.02). The amount of Ku80 expression in ALL was moderately correlated with peripheral white blood cell counts, but not with Ki67 labeling index. High Ku80 expressers (higher than the mean of all patients with ALL) tended to respond poorly to therapy: Only 22% of high Ku80 expressers achieved durable complete remission compared to 62% of low expressers.


CONCLUSIONS
Our study suggests that Ku80 might contribute to generally poor prognoses in adult ALL.
Chen
Tsai-Yun
TY
Section of Hematology/Oncology, Department of Internal Medicine, National Cheng Kung University Hospital, Tainan, Taiwan. teresa@mail.ncku.edu.tw
Chen
Jiann-Shiuh
JS
Su
Wu-Chou
WC
Wu
Ming-Shiuan
MS
Tsao
Chao-Jung
CJ
D000293:Adolescent; D000328:Adult; D034961:Antigens, Nuclear / Q000096:biosynthesis* / Q000235:genetics; D045744:Cell Line, Tumor; D002648:Child; D002675:Child, Preschool; D004260:DNA Repair / Q000235:genetics*; D004268:DNA-Binding Proteins / Q000096:biosynthesis* / Q000235:genetics; D015973:Gene Expression Regulation, Leukemic; D006801:Humans; D007223:Infant; D019394:Ki-67 Antigen / Q000096:biosynthesis / Q000235:genetics; D000072200:Ku Autoantigen; D015451:Leukemia, Lymphocytic, Chronic, B-Cell / Q000235:genetics* / Q000473:pathology; D007963:Leukocytes, Mononuclear / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000235:genetics* / Q000473:pathology; D011379:Prognosis; D012333:RNA, Messenger / Q000096:biosynthesis / Q000235:genetics
D034961:Antigens, Nuclear; D004268:DNA-Binding Proteins; D019394:Ki-67 Antigen; D012333:RNA, Messenger; C000606509:Xrcc6 protein, human; D000072200:Ku Autoantigen