目的 观察慢性淋巴细胞白血病(CLL)患者外周血中p53基因突变情况,并探讨其临床意义.方法 采用PCR联合测序技术检测80例CLL患者及10例健康体检者外周血中的p53基因,CLL患者中25例应用FC方案(氟达拉滨25 mg/m2,环磷酰胺250 mg/m2,第1～3天静滴)化疗,28 d为1个疗程,治疗2～6个疗程.结果 80例CLL患者中12例(15.0％)检测到p53基因突变,其中错义突变11例、无义突变1例,未检测到插入和缺失；突变位点均发生在外显子(exon)5～9,其中发生在exon 5 2例、exon 6 3例、exon 7 1例、exon 8 5例、exon 9 1例,exon2～4、exon 10、exon 11未检测到突变.健康体检者中均未检测到p53基因突变.二者p53基因突变率比较,P＜0.05.p53基因突变与Binet分期、p53基因缺失、IgVH突变有关(P均＜0.05).80例CLL患者中25例化疗后CR5例、PR 11例,总反应率(OR)为64.0％；p53基因突变者OR为14.3％,低于p53基因无突变者的83.3％(P＜0.05).结论 CLL患者外周血中存在p53基因突变,其可作为预后判定的指标.%Objective To investigate the mutation of p53 and its clinical significance in peripheral blood of patients with chronic lymphocytic leukemia ( CLL). Methods p53 gene mutations were detected by polymerase chain reaction (PCR) and subsequent sequencing in peripheral blood of 80 CLL patients and 10 healthy controls. FC regimens (fludara-bine 25 mg/m2, cyclophosphamide 250 mg/m2, intravenous infusion for 3 days) were repeated for 2 to 6 cycles at four weeks intervals were administrated in 25 patients. Results Among 80 patients, 12 (15.0%) cases had p53 mutations, including 11 cases of missense mutations and 1 case of nonsense mutation. No insertions or insertions were detected. Mutations were discovered in exon 5 to 9, including 2 cases of exon 5, 3 cases of exon 6, 1 case of exon 7, 5 cases of exon 8 and 1 case of exon 9. No mutations were detected in 10 healthy controlsor the remaining exons in CLL patients (all P < 0.05 ). Patients with p53 mutations displayed higher incidence of advanced stage, p53 deletions, and unmutated IgVH ( all P < 0.05 ) . In 25 patients treated with FC regimens, 5 cases achieved CR and 11 cases obtained PR (OR, overall response 64.0% ). Patients with p53 mutations showed lower incidence of overall response than patients without mutations (14. 3% vs 83. 3% , P <0.05). Conclusions p53 mutations occur in peripheral blood of patients with CLL. Our data confirm a role for p53 mutations as an important prognostic indicator in CLL.
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