Dong Hua-Jie, Fang Cheng, Wang Li, Fan Lei, Xu Ji, Wu Jia-Zhu, Lu Ting-Xun, Li Jian-Yong, Xu Wei
Department of Hematology, First Affiliated Hospital of Nanjing Medical University, Jiangsu Province Hospital, Nanjing, 210029, China.
Med Oncol. 2014 Apr;31(4):908. doi: 10.1007/s12032-014-0908-5. Epub 2014 Mar 11.
Previous studies have investigated the associations between TP53 mutations and codon 72 polymorphisms and prognosis in chronic lymphocytic leukemia (CLL). However, the joint effect of TP53 mutations and TP53 codon 72 polymorphisms on CLL prognosis remains uncertain. We used direct sequencing to detect TP53 mutations and codon 72 genotype in 207 patients with CLL. The Pro/Pro genotype was associated with an increased incidence of TP53 mutations and deletion, but had no apparent effect on biological tumor behavior or clinical response. Compared to patients with wild-type p53, patients with TP53 mutations and the Pro72 allele (Arg/Pro + Pro/Pro genotypes) were associated with unmutated immunoglobulin heavy-chain variable region status and chemorefractoriness. Overall survival (OS) in the entire patient group was differed significantly between patients with TP53 mutations and either the Pro72 allele or Arg/Arg homozygotes (P = 0.014). Notably, patients with TP53 mutation and the Pro72 allele experienced a 23.7-fold increase in hazard ratio (95% CI 3.38-165.9; P = 0.001) for OS compared with patients with wild-type p53 and those with the Arg/Arg genotype. The TP53 Pro72 allele potentially increases the prognostic significance of TP53 mutations in CLL.
既往研究已对慢性淋巴细胞白血病（CLL）中TP53突变、密码子72多态性与预后之间的关联进行了调查。然而，TP53突变与TP53密码子72多态性对CLL预后的联合影响仍不明确。我们采用直接测序法检测了207例CLL患者的TP53突变及密码子72基因型。Pro/Pro基因型与TP53突变及缺失的发生率增加相关，但对肿瘤生物学行为或临床反应无明显影响。与野生型p53患者相比，携带TP53突变及Pro72等位基因（Arg/Pro + Pro/Pro基因型）的患者与免疫球蛋白重链可变区未突变状态及化疗耐药相关。整个患者组中，携带TP53突变及Pro72等位基因或Arg/Arg纯合子的患者总生存期（OS）与TP53未突变患者有显著差异（P = 0.014）。值得注意的是，与野生型p53及Arg/Arg基因型患者相比，携带TP53突变及Pro72等位基因的患者OS的风险比增加了23.7倍（95%CI 3.38 - 165.9；P = 0.001）。TP53 Pro72等位基因可能增加了TP53突变在CLL中的预后意义。
