p16基因缺失在儿童与成人急性B淋巴细胞白血病的临床意义

Comparison of clinical implications of p16 deletion in childhood and adult B-lineage acute lymphoblastic leukemia

目的探讨p16基因缺失对儿童与成人急性B淋巴细胞白血病（B—ALL）预后的影响。方法采用流式细胞术、G显带核型分析和问期荧光原位杂交（I-FISH）技术，对73例儿童和56例成人B—ALL患者进行免疫学和细胞遗传学检测，并回顾分析其临床资料。结果I-FISH检测发现儿童组患者中p16基因纯合性缺失、杂合性缺失和无缺失的发生率分别为24．7％（18例）、6．8％（5例）、68．5％（50例），成人组患者分别为14．3％（8例）、8．9％（5例）、76．8％（43例）；儿童组与成人组p16基因缺失发生率比较差异无统计学意义（P=0．338）；分别对两组患者中p16基因缺失与无缺失者临床特征进行比较，外周血WBC、骨髓原始细胞比例、染色体核型、髓外浸润发生率、第1次化疗完全缓解率等方面差异无统计学意义（P〉0．05）。分别有2例儿童和成人患者初治时无p16基因缺失，复发时检测结果显示p16基因缺失。儿童组p16基因缺失者与无缺失者的总生存（OS）率分别为45．3％和79．8％（P=0．006），成人组分别为7．7％和22．6％（P=0．002）；儿童组p16基因缺失者与无缺失者的无事件生存（EFS）率分别为33．5％和58．1％（P：0．008），成人组分别为0和10．9％（P〈0．001），差异均有统计学意义。儿童标危组p16基因缺失者与无缺失者OS率分别为46．8％和89．3％（P=0．015），EFS率分别为40．9％和82．1％（P=0．007）；儿童高危组p16基因缺失者与无缺失者0s率分别为41．7％和67．4％（P=0．193），EFS率分别为25．0％和25．6％（P=0．305）；成人标危组p16基因缺失者与无缺失者OS率分别为20．0％和46．9％（P=0．092），EFS率分别为0和25．0％（P=0．062）；成人高危组p16基因缺失者与无缺失者0s率分别为0和12．4％（P〈0．01），EFS率分别为0和4．8％（P〈0．001）。结论p16基因缺失的儿童和成人B—ALL患者预后相对较差，明确p16基因缺失状态对于评估预后和指导临床治疗有重要意义。

Objective To investigate and compare the clinical implications of p16 deletion in child- hood and adult B-lineage acute lymphoblastic leukemia （B-ALL）. Methods A total of 129 cases of de novo childhood （73 cases） and adult （56 cases ） B-ALL were examined genetically and immunologically using G-banding teehniqhe,interphase fluorescence in situ hybridization （I-FISH） and immunophenotyping by flow cytometry, and their clinical data were retrospectively analyzed. Results Of 73 childhood cases, the prevalences of homozygous deletion, hemizygous deletion and no deletion of p16 were 24.7% （ 18 cases） , 6.8% （5 cases） and 68.5% （50 cases） respectively, and of 56 adult cases, the incidences as of 14.3% （8 cases）, 8.9% （5 cases） and 76.8% （43 cases） respectively. The incidence of p16 deletion between the two groups had no significant difference （P =0. 338）. In both groups, patients with or without p16 deletion had no significant difference in terms of white blood cells （WBC） count at diagnosis, BM blast percentage, chromosome karyotype, extra-infiltration and CR1 rate. Of note, there were 2 cases, each in childhood and adult, showed no deletion at the time of diagnosis, their p16 deletions occurred at relapse. The deletion of p16 was associated with poor overall survival and event-free survival （EFS） in both childhood and adults. According to the standard of NCI risk stratification, we divided patients of two groups into standard and high risk category respectively, and performed further analysis. The significance of different risk category in chil- dren and adults was disparity. The overall survival （OS） rates of deletion and no deletion of p16 were 45.3% and 79.8% （P =0.006） in children, and 7.7% and 22.6% （P =0. 002） in adults, respectively. EFS rates of deletion and no deletion of p16 were 33.5% and 58.1% （P =0. 008） in children, and 0 and 10.9% （ P 〈0.01 ） in adults, respectively. Of the standard risk category in children, OS rates of deletion and no de- letion of p16 were 46.8% and 89.3% （P = 0. 015 ） respectively, and EFS rates of deletion and no deletion of p16 as of 40.9% and 82.1% （P = O. 007） respectively. Of the high risk category in children, OS rates of deletion and no deletion of p16 were 41.7% and 67.4% （P = 0. 193 ） respectively, and EFS rates of deletion and no deletion of p16 were 25.0% and 25.6% （P = 0. 505） respectively. Of the standard risk category in adults, OS rates of deletion and no deletion of p16 were 20.0% and 46.9% （P =0. 092） respectively, and EFS rates of deletion and no deletion of p16 were 0 and 25.0% （P = 0. 062） respectively. Of the high risk category in adults, OS rates of deletion and no deletion of p16 were 0 and 12.4% （P 〈0.001 ） respectively, and EFS rate of deletion and no deletion of p16 was 0 and 4.8% （P 〈 0. 001 ）, respectively. Conclusions This study indicated that deletion of p16 was associated with poor prognosis in both childhood and adult B- ALL, which highlighted an important significance to define the status of p16 in both childhood and adult B- ALL for predicting prognosis and guiding clinical intervention.