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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.
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This work was supported by the National Natural Science Foundation of China (81170486, 81170485), Scientific Research Foundation from the Ministry of Education of China (43-NJYKDX-3), Jiangsu Province's Medical Elite Program (RC2011168), Key Project of Jiangsu Province Health Agency (K201107), “Liu Da Ren Cai Gao Feng” Project (2012-WS-017) and A Project Funded by the Priority Academic Program Development of Jiangsu Higher Education Institute (JX10231801).