title: Clinical significance of down-regulated cylindromatosis gene in chronic lymphocytic leukemia.
abstract: Loss of cylindromatosis gene (CYLD) expression has been observed in various cancers, including chronic lymphocytic leukemia (CLL). As a deubiquitination enzyme, CYLD regulates the proliferation, development and activation of lymphoid cells. Here we determined the CYLD mRNA expression by quantitative polymerase chain reaction (PCR) in 125 patients with CLL. CYLD was considerably down-regulated in CLL cells compared to normal B cells. Low CYLD expression was associated with unmutated status of the immunoglobulin heavy-chain variable-region (IGHV) gene (p = 0.0018) and CD38 positivity (p = 0.0499). Patients with high CYLD expression showed a trend toward improved overall survival (OS) (10-year OS: CYLD high: 94.74%, CYLD low: 52.71%; p = 0.0534). For patients with mutated IGHV gene, high CYLD was also associated with better OS (10-year OS: CYLD high: 100%, CYLD low: 66.67%; p = 0.0547). In conclusion, low CYLD expression identifies a subgroup of patients with CLL with inferior outcome, indicating the role of CYLD as a tumor suppressor in the pathogenesis of CLL.
authors.affiliation: Department of Hematology, The First Affiliated Hospital of Nanjing Medical University , Nanjing , P.R. China.
authors.forename: Wei
authors.initials: W
authors.lastname: Wu
authors.forename: Huayuan
authors.initials: H
authors.lastname: Zhu
authors.forename: Yuan
authors.initials: Y
authors.lastname: Fu
authors.forename: Wenyi
authors.initials: W
authors.lastname: Shen
authors.forename: Jiadai
authors.initials: J
authors.lastname: Xu
authors.forename: Kourong
authors.initials: K
authors.lastname: Miao
authors.forename: Ming
authors.initials: M
authors.lastname: Hong
authors.forename: Wei
authors.initials: W
authors.lastname: Xu
authors.forename: Peng
authors.initials: P
authors.lastname: Liu
authors.forename: Jianyong
authors.initials: J
authors.lastname: Li
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use; D000074749:Deubiquitinating Enzyme CYLD; D015536:Down-Regulation; D005260:Female; D015973:Gene Expression Regulation, Leukemic; D006801:Humans; D007143:Immunoglobulin Heavy Chains / Q000235:genetics; D015451:Leukemia, Lymphocytic, Chronic, B-Cell / Q000188:drug therapy / Q000235:genetics* / Q000401:mortality* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D009154:Mutation; D009367:Neoplasm Staging; D011379:Prognosis; D012333:RNA, Messenger / Q000235:genetics; D025521:Tumor Suppressor Proteins / Q000235:genetics* / Q000378:metabolism
chemical_list: D007143:Immunoglobulin Heavy Chains; D012333:RNA, Messenger; D025521:Tumor Suppressor Proteins; C409984:CYLD protein, human; D000074749:Deubiquitinating Enzyme CYLD