[1]张军伟.成人与儿童急性淋巴细胞白血病免疫表型、染色体和分子遗传学异常分析[J].新乡医学院学报,2022,39(1):060-66.[doi:10.7683/xxyxyxb.2022.01.013]
　ZHANG Junwei.Analysis of immunophenotype,chromosomal and molecular genetic abnormalities in adults and children with acute lymphoblastic leukemia[J].Journal of Xinxiang Medical University,2022,39(1):060-66.[doi:10.7683/xxyxyxb.2022.01.013]
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成人与儿童急性淋巴细胞白血病免疫表型、染色体和分子遗传学异常分析
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《新乡医学院学报》[ISSN:1004-7239/CN:41-1186/R]

卷:
39
期数:
2022年1
页码:
060-66
栏目:
临床研究
出版日期:
2022-01-05

文章信息/Info

Title:
Analysis of immunophenotype,chromosomal and molecular genetic abnormalities in adults and children with acute lymphoblastic leukemia
作者:
张军伟
（焦作市第二人民医院检验科，河南　焦作　454000）
Author(s):
ZHANG Junwei
(Department of Clinical Laboratory,the Second People′s Hospital of Jiaozuo City,Jiaozuo 454000,Henan Province,China)
关键词:
急性淋巴细胞白血病; 免疫表型; 染色体; 分子遗传学
Keywords:
acute lymphoblastic leukemiaimmunophenotypechromosomemolecular genetics
分类号:
R47
DOI:
10.7683/xxyxyxb.2022.01.013
文献标志码:
A
摘要:
目的　分析急性淋巴细胞白血病（ALL）患者免疫表型、染色体和分子遗传学异常。方法　选择2014年1月至2015年1月于焦作市第二人民医院收治的139例ALL患者为研究对象，按年龄将患者分为儿童组（≤14岁，n=57）和成人组（>14岁，n=82）。检测并分析患者的免疫表型、染色体核型及分子遗传学特征；所有患者随访5 a，记录患者完全缓解（CR）、复发、总生存期（OS）、中位OS等。采用Cox模型分析ALL患者复发、死亡风险的影响因素，采用 Kaplan-Meier 法绘制生存曲线，采用log-rank检验进行生存分析。结果　139例ALL患者均进行免疫表型检查，其中急性B淋巴细胞白血病（B-ALL）患者115例（82.74%），急性T淋巴细胞白血病（T-ALL）患者18例（12.96%），非T非B细胞型急性淋巴细胞白血病（N-ALL）3例（2.15%），T/B双表达急性淋巴细胞白血病（急性混合型）3例（2.15%）。成人组与儿童组患者的免疫表型比较差异无统计学意义（P>0.05）。T-ALL患者的干/祖细胞标志CD34、人白细胞DR抗原（HLA-DR）阳性率明显低于B-ALL患者（P<0.05）。Kaplan-Meier分析显示，含有脯氨酸合成途径必须的基因B（pro-B）型患者的中位OS未达到，普通B细胞（com-B）型、前B细胞（pre-B）型、T-ALL患者的中位OS分别为41、45、22个月；log-rank检验显示，T-ALL患者的中位OS显著短于com-B型、pre-B型患者（P<0.05）。139例ALL患者均进行染色体核型分析，其中正常核型72例（51.80%），异常核型67例（48.20%）。成人组患者中正常核型34例（41.46%），异常核型48例（58.54%）；儿童组患者中正常核型38例（66.67%），异常核型19例（33.33%）；儿童组患者异常核型比例显著低于成人组（P<0.05）。儿童组和成人组t(922)核型患者分别占3.51%（2/57）、21.95%（18/82），儿童组和成人组t(814)核型患者分别占0.00%（0/57）、7.37%（6/82），儿童组t(922)、t(814)核型患者比例显著低于成人组（P<0.05）。Kaplan-Meier分析显示，正常核型患者的中位OS未达到，t(922)、亚二倍体、复杂核型及其他类型的核型异常患者的中位OS显著低于正常核型患者（P<0.05）。单因素Cox分析显示，t(922)核型异常患者死亡风险是正常核型患者的4.008倍，其他核型异常患者死亡风险是正常核型的2.658倍。139例ALL患者均进行分子生物学检查，未检出融合基因者93例（66.90%），检出融合基因者46例（33.10%）。儿童组患者融合基因检出率显著低于成人组（χ2=4.617，P<0.05）。Kaplan-Meier分析显示，未检出融合基因患者的中位OS未达到，BCR/ABL融合基因患者的中位OS为14.25个月，未检出融合基因患者的中位OS显著长于BCR/ABL融合基因患者（P<0.05）。儿童组和成人组患者的CR率分别为98.25%（56/57）、82.93%（68/82），儿童组患者的CR率显著高于成人组（P<0.05）。82例成人患者中，低危、标危、高危患者的CR率分别为0.00%（0/0）、87.88%（58/66）、62.50%（10/16），标危患者CR率显著高于高危患者（P<0.05）。57例儿童患者中，低危、标危、高危患儿的CR率分别为100.00%（10/10）、100.00%（41/41）、83.33%（5/6）；高危患儿的CR率显著低于标危患儿（P<0.05）；高危患儿的CR率低于低危患儿，但差异无统计学意义（P>0.05）；标危与低危患儿的CR率比较差异无统计学意义（P>0.05）。儿童组和成人组CR患者的复发率分别为21.43%（12/56）、72.06%（49/68），儿童组CR患者的复发率显著低于成人组（P<0.05）。68例CR成人患者中，低危、标危、高危患者的复发率分别为0.00%（0/0）、74.14%（43/58）、60.00%（6/10）；标危成人CR患者的复发率高于高危成人患者，但差异无统计学意义（P>0.05）。56例CR患儿中，低危、标危、高危患儿的复发率分别为10.00%（1/10）、19.51%（8/41）、60.00%（3/5）；高危CR患儿的复发率显著高于低危和标危患儿（P<0.05）；标危CR患儿的复发率高于低危患儿，但差异无统计学意义（P>0.05）。儿童组和成人组患者的OS分别为（36.26±5.69）、（18.85±4.69）个月，儿童组患者的OS显著长于成人组（P<0.05）。标危、高危成人患者的OS分别为（19.00±4.16）、（13.00±3.59）个月，高危成人患者的OS显著短于标危患者（P<0.05）。低危、标危、高危患儿的OS分别为（43.56±4.15）、（38.16±3.28）、（19.10±2.58）个月；低危患儿的OS显著长于标危患儿（P<0.05），低危和标危患儿的OS显著长于高危患儿（P<0.05）。结论　与ALL成人患者相比，ALL儿童患者核型异常和分子遗传学异常发生率较低，CR率较高，预后较好；骨髓细胞形态学-免疫学-细胞遗传学-分子生物学分型（MICM分型）对ALL患者的预后判断具有一定价值。
Abstract:
Objective　To analyze the immunophenotype,chromosomal and molecular genetic abnormalities in adults and children with acute lymphoblastic leukemia (ALL).Methods　A total of 139 ALL patients treated in the Second People′s Hospital of Jiaozuo City from January 2014 to January 2015 were selected as the research subjects,and the patients were divided into children group (≤14 years old,n=57) and adult group (>14 years old,n=82).The immunophenotype,chromosome karyotype and molecular genetic characteristics of the patients were detected and analyzed.All patients were followed up for 5 years,and the complete remission (CR),recurrence,overall survival (OS) and median OS were recorded.The influencing factors of recurrence and death of ALL patients were analyzed by Cox model.The survival curves were drawn by Kaplan-Meier method and the survival analysis was performed by log-rank test.Results　The immunophenotype detection was performed in the 139 patients with ALL,including 115(82.74%) patients with acute B-lymphoblastic leukemia (B-ALL),18(12.96%) patients with acute T-lymphoblastic leukemia (T-ALL),3 (2.15%) patients with null acute lymphocytic leukemia (N-ALL) and 3(2.15%) patients with T/B double expression acute lymphoblastic leukemia (acute mixed type).There was no significant difference in immunophenotype between adult group and children group (P>0.05).The positive rates of stem/progenitor cell marker CD34 and human leukocyte antigen DR (HLA-DR) in patients with T-ALL were significantly lower than those in patients with B-ALL (P<0.05).Kaplan Meier analysis showed that the median OS of patients with common B cell (com-B),pre-B cell (pre-B) and T-ALL was 41,45 and 22 months,respectivelybut the median OS of patients with gene B containing the proline (pro-B) was not reached.Log-rank test showed that the median OS of patients with T-ALL was significantly shorter than that of patients with com-B and pre-B (P<0.05).The chromosome karyotypes of 139 patients with ALL were analyzed,including 72 cases of normal karyotype (51.80%) and 67 cases of abnormal karyotype (48.20%).In the adult group,34 cases (41.46%) had normal karyotype and 48 cases (58.54%) had abnormal karyotype.In the children group,38 cases (66.67%) had normal karyotype and 19 cases (33.33%) had abnormal karyotype.The proportion of abnormal karyotype in the children group was significantly lower than that in the adult group (P<0.05).The patients with T(922) karyotype in the children group and the adult group accounted for 3.51% (2/57) and 21.95% (18/82),respectivelyand the patients with T(814) karyotype in the children group and the adult group accounted for 0% (0/57) and 7.37% (6/82),respectively.The proportion of patients with t(922) and t(814) karyotypes in the children group was significantly lower than that in the adult group (P<0.05).Kaplan Meier analysis showed that the median OS of patients with normal karyotype was not reached,and the median OS of patients with t(922),sub diploid,complex karyotype and other abnormal karyotype was significantly lower than that of patients with normal karyotype (P<0.05).The univariate Cox analysis showed that the death risk of patients with abnormal T(922) karyotype was 4.008 times higher than that of patients with normal karyotype,and that of patients with other abnormal karyotypes was 2.658 times higher than that of patients with normal karyotype.The molecular biological examination was performed in 139 patients with ALL,including 93 patients (66.90%) without fusion genes and 46 patients (33.10%) with fused genes.The detection rate of fusion gene in the children group was significantly lower than that in the adults group (χ2=4.617,P<0.05).Kaplan-Meier analysis showed that the median OS of patients without fusion gene was not reached,and the median OS of patients with BCR/ABL fusion gene was 14.25 months.The median OS of patients without fusion gene was significantly higher than that of patients with BCR/ABL fusion gene (P<0.05).The CR rate of children and adults was 98.25% (56/57) and 82.93% (68/82),respectivelythe CR rate of children was significantly higher than that of adults (P<0.05).Among the 82 adult patients,the CR rate of the low-risk,standard-risk and high-risk patients was 0.00% (0/0),87.88% (58/66) and 62.50% (10/16),respectivelythe CR rate of standard risk patients was significantly higher than that of the high-risk patients (P<0.05).Among the 57 children,the CR rate of the low-risk,standard-risk and high-risk children was 100% (10/10),100% (41/41) and 83.33% (5/6),respectively.Conclusion　Compared with the adult patients with ALL,the children with ALL have lower incidence of abnormal karyotype and molecular genetics,higher CR rate and better prognosis.The bone marrow cell morphology-immunology-cytogenetics-molecular biology typing (MICM typing) has a certain value in the prognosis judgment of ALL patients.

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更新日期/Last Update: 2022-01-05