摘要
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% ）. Pa- tients 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.
出处
《山东医药》
CAS
2012年第34期1-4,共4页
Shandong Medical Journal
基金
国家自然科学基金资助项目(81170489)
江苏省自然科学基金资助项目(BK2010287)
