Kochethu Geothy, Delgado Julio, Pepper Chris, Starczynski Jane, Hooper Laura, Krishnan Satish, Fegan Christopher, Pratt Guy
Department of Haematology, Heart of England NHS Trust, Bordesley Green East, Birmingham, UK.
Leuk Res. 2006 Sep;30(9):1113-8. doi: 10.1016/j.leukres.2005.12.014. Epub 2006 Feb 3.
Chronic lymphocytic leukaemia (CLL) is characterised by the accumulation of mature B lymphocytes. Defects in the tumour suppressor gene p53 pathway are known to be important in CLL and p53 inactivation is associated with a particularly aggressive form of CLL. A single nucleotide polymorphism (SNP) in codon 72 of TP53 leads to a single amino acid change leading to a change in apoptotic potential and alters prognosis in squamous carcinomas. A polymorphism within intron 6 of TP53 has been postulated to alter the susceptibility to lung cancer. Our study looked at the influence of these two polymorphisms in a cohort of approximately 200 CLL patients. The codon 72 polymorphism A2/A2 genotype (homozygous arginine) was associated with an increased susceptibility to CLL and CD38 negativity but did not appear to influence other biological behaviour or clinical response. The intron 6 polymorphism A2/A2 genotype was strongly associated with early stage disease, CD38 negativity and a longer time to first treatment. The effect on time to treatment did not retain significance in multivariate analysis and the polymorphism did not predict for overall survival (OS). Detailed investigation of the complete TP53 genotype is warranted to further characterise the role of SNPs in p53 and their influence on CLL.
慢性淋巴细胞白血病（CLL）的特征是成熟B淋巴细胞的积累。已知肿瘤抑制基因p53通路的缺陷在CLL中很重要，并且p53失活与一种特别侵袭性的CLL形式相关。TP53第72密码子的单核苷酸多态性（SNP）导致单个氨基酸改变，从而导致凋亡潜能的改变，并改变鳞状细胞癌的预后。有人推测TP53内含子6内的多态性会改变肺癌易感性。我们的研究观察了这两种多态性对一组约200例CLL患者的影响。第72密码子多态性A2/A2基因型（纯合精氨酸）与CLL易感性增加和CD38阴性相关，但似乎不影响其他生物学行为或临床反应。内含子6多态性A2/A2基因型与疾病早期、CD38阴性以及首次治疗时间延长密切相关。在多变量分析中，对治疗时间的影响不再具有显著性，并且该多态性不能预测总生存期（OS）。有必要对完整的TP53基因型进行详细研究，以进一步明确SNP在p53中的作用及其对CLL的影响。
