一例白血病患者HLA位点杂合性丢失的分析  

Analysis of loss of heterozygosity at HLA loci in a patient with leukemia

作　　者：王炜[1,2] 王芳 董丽娜[1,2] 陈男英 何亿镇[1,2] 章伟 何吉[1,2] 朱发明 Wang Wei;Wang Fang;Dong Lina;Chen Nanying;He Yizhen;Zhang Wei;He Ji;Zhu Faming(Blood Center of Zhejiang Province,Key Laboratory of Blood Safety Research of Zhejiang Province,Hangzhou,Zhejiang 310052,China)

机构地区：[1]浙江省血液中心,杭州310052 [2]浙江省血液安全研究重点实验室,杭州310052

出　　处：《中华医学遗传学杂志》2022年第3期338-342,共5页Chinese Journal of Medical Genetics

基　　金：浙江省科技厅公益技术应用研究(LGF19H100001);浙江省医药卫生科学研究基金(2020RC053和2021KY651)。

摘　　要：目的分析1例白血病患者人类白细胞抗原(human leukocyte antigen,HLA)杂合性丢失情况。方法采用聚合酶链反应序列特异性寡核苷酸探针法和聚合酶链反应测序方法对患者移植后外周血、头发毛囊、口腔黏膜拭子及其父母外周血进行HLA分型。采用23位点短串联重复序列(short tandem repeat,STR)测定试剂盒和本实验室建立的HLA区域内的6个STR位点方法对患者移植后的外周血、口腔黏膜拭子及其父母外周血进行STR位点检测。结果患者经父亲源单倍型造血干细胞移植后,外周血标本HLA基因型与父亲完全一致。患者头发毛囊标本HLA结果为HLA-A*02:01,24:02,C*03:03,03:04,B*13:01,15:01,DRB1*08:03,12:02,DQB1*03:01,06:01。口腔黏膜拭子为HLA纯合子,只存在父亲单倍型HLA-A*24:02-C*03:03-B*15:01-DRB1*08:03-DQB1*06:01,丢失了母亲单倍型HLA-A*02:01-C*03:04-B*13:01-DRB1*12:02-DQB1*03:01。患者移植后外周血23个STR位点与父亲完全一致。口腔黏膜拭子23位点短串联重复位点无丢失,但6号染色体上HLA区域的6个STR位点至少有4个发生了丢失。结论发现1例单倍型造血干细胞移植白血病患者的口腔黏膜拭子发生HLA杂合性丢失。Objective To detect loss of heterozygosity(LOH)at human leukocyte antigen(HLA)loci in a Chinese patient with leukemia after haploidentical hematopoietic stem cell transplantation.Methods HLA genotyping was carried out on peripheral blood,hair follicle and buccal swab samples derived from the patient after the transplantation as well as peripheral blood samples from his parents by using PCR-sequence specific oligonucleotide probe method and PCR-sequence based typing method.Short tandem repeat(STR)loci were detected by using a 23 site STR assay kit and a self-developed 6 STR loci assay for the HLA regions.Results After the transplantation,the HLA genotype of the peripheral blood sample of the patient was identical to his father.The patient was HLA-A*02:01,24:02,C*03:03,03:04,B*13:01,15:01,DRB1*08:03,12:02,DQB1*03:01,06:01 for his hair follicle specimen.However,homozygosity of the HLA loci was found in his buccal swab sample.Only the HLA-A*24:02-C*03:03-B*15:01-DRB1*08:03-DQB1*06:01 haplotype from his father’s was present,while the HLA-A*02:01-C*03:04-B*13:01-DRB1*12:02-DQB1*03:01 haplotype from his mother was lost.After the transplantation,the alleles of the 23 STR sites in the patient’s peripheral blood sample were consistent to his father,with no allelic loss detected in his buccal swab sample.However,at least 4 STR loci in the HLA region were lost in his buccal swab sample.Conclusion LOH at the HLA loci has been detected in the buccal swab sample of a patient with leukemia who received haploidentical hematopoietic stem cell transplantation.

关 键 词：HLA杂合性丢失 白血病患者 HLA基因分型 造血干细胞移植 

分 类 号：R733.7[医药卫生—肿瘤]