Expression level of DEK in chronic lymphocytic leukemia is regulated by fludarabine and Nutlin-3 depending on p53 status.
Human oncogene DEK has been shown to be upregulated in a number of neoplasms. The purpose of this study was to investigate DEK expression level in chronic lymphocytic leukemia (CLL), analyze the correlation between DEK expression and CLL prognostic markers, and characterize the role of DEK in the response to either chemotherapeutic drugs or nongenotoxic activators of the p53 pathway. DEK mRNA was evaluated by real-time quantitative reverse transcriptase-polymerase chain reaction (qPCR), and primary CLL samples were treated in vitro with either fludarabine or Nutlin-3 to explore the interaction of p53 status and DEK mRNA expression. The median expression levels of DEK mRNA were 6.792 × 10 (-2)  (1.438 × 10 (-2) -3.201 × 10 (-1) ) in 65 patients with CLL. A marked increase of DEK mRNA expression was observed in the CLL patients with unmutated immunoglobulin heavy chain variable (IGHV) gene (p = 0.025), CD38-positive (p = 0.047), del(17p13) (p = 0.006). Both fludarabine and Nutlin-3 significantly downregulated DEK in the primary CLL cells which were with normal function of p53, or without deletion or mutation of p53 (p = 0.042, p = 0.038; p = 0.021, p = 0.017; p = 0.037, p = 0.017). However, the downregulation of DEK was not observed in the primary CLL cells which were with dysfunction of p53, or with deletion or mutation of p53 (p = 0.834, p = 0.477; p = 0.111, p = 0.378; p = 0.263, p = 0.378). These data show that DEK might be applied for the assessment of prognosis in patients with CLL, and fludarabine and Nutlin-3 regulate DEK expression depended on p53 status.
Department of Hematology, The First Affiliated Hospital of Nanjing Medical University, Jiangsu Province Hospital, Nanjing, PR China.
Dong-Mei
DM
Wang
Ling
L
Liu
Lei
L
Fan
Zhi-Jian
ZJ
Zou
Li-Na
LN
Zhang
Shu
S
Yang
Jian-Yong
JY
Li
Wei
W
Xu
D051997:ADP-ribosyl Cyclase 1 / Q000032:analysis; D000368:Aged; D000369:Aged, 80 and over; D000970:Antineoplastic Agents / Q000494:pharmacology; D002868:Chromosomal Proteins, Non-Histone / Q000235:genetics / Q000378:metabolism*; D005260:Female; D006801:Humans; D007093:Imidazoles / Q000494:pharmacology*; D007143:Immunoglobulin Heavy Chains / Q000235:genetics; D015451:Leukemia, Lymphocytic, Chronic, B-Cell / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D009698:Nucleoproteins / Q000378:metabolism; D015513:Oncogene Proteins / Q000235:genetics / Q000378:metabolism*; D010879:Piperazines / Q000494:pharmacology*; D000075223:Poly-ADP-Ribose Binding Proteins; D011379:Prognosis; D012333:RNA, Messenger / Q000096:biosynthesis; D014407:Tumor Cells, Cultured; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism*; D014740:Vidarabine / Q000031:analogs & derivatives* / Q000494:pharmacology; D051746:ZAP-70 Protein-Tyrosine Kinase / Q000032:analysis
D000970:Antineoplastic Agents; D002868:Chromosomal Proteins, Non-Histone; C084738:DEK protein, human; D007093:Imidazoles; D007143:Immunoglobulin Heavy Chains; D009698:Nucleoproteins; D015513:Oncogene Proteins; D010879:Piperazines; D000075223:Poly-ADP-Ribose Binding Proteins; D012333:RNA, Messenger; D016159:Tumor Suppressor Protein p53; C482205:nutlin 3; D051746:ZAP-70 Protein-Tyrosine Kinase; D051997:ADP-ribosyl Cyclase 1; D014740:Vidarabine; C024352:fludarabine