Relapse of leukemia with loss of mismatched HLA resulting from uniparental disomy after haploidentical hematopoietic stem cell transplantation.
Relapse of leukemia with loss of mismatched HLA resulting from uniparental disomy after haploidentical hematopoietic stem cell transplantation.
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DOI：
10.1182/blood-2009-11-254284
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发表时间：
2010-04
期刊：
影响因子：
20.3
通讯作者：
I. B. Villalobos;Yoshiyuki Takahashi;Y. Akatsuka;H. Muramatsu;N. Nishio;A. Hama;H. Yagasaki;H. Saji;Motohiro Kato;S. Ogawa;S. Kojima
中科院分区：
文献类型：
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作者：
I. B. Villalobos;Yoshiyuki Takahashi;Y. Akatsuka;H. Muramatsu;N. Nishio;A. Hama;H. Yagasaki;H. Saji;Motohiro Kato;S. Ogawa;S. Kojima
我们研究了人类白细胞抗原（HLA）表达的白血病细胞来源于患者在诊断和造血干细胞移植（HSCT）后复发，使用流式细胞术位点特异性抗体。HLA半相合HSCT后复发的3例患者中有2例在复发时表现出白血病细胞中HLA等位基因的丢失;另一方面，在HLA相合HSCT后复发的6例患者中未观察到HLA等位基因的丢失。分选白血病细胞的单核苷酸多态性阵列分析进一步揭示了拷贝数中性杂合性丢失，即6号染色体短臂上获得性单亲二体性，导致错配HLA单倍型的完全丢失。这些结果表明，不匹配的HLA等位基因的丢失逃避免疫监视可能是HLA半相合HSCT后复发的一个重要机制。因此，在输注供者淋巴细胞前，应检查复发白血病细胞上的HLA错配情况。
We investigated human leukocyte antigen (HLA) expression on leukemic cells derived from patients at diagnosis and relapse after hematopoietic stem cell transplantation (HSCT) using flow cytometry with locus-specific antibodies. Two of 3 patients who relapsed after HLA-haploidentical HSCT demonstrated loss of HLA alleles in leukemic cells at relapse; on the other hand, no loss of HLA alleles was seen in 6 patients who relapsed after HLA-identical HSCT. Single-nucleotide polymorphism array analyses of sorted leukemic cells further revealed the copy number-neutral loss of heterozygosity, namely, acquired uniparental disomy on the short arm of chromosome 6, resulting in the total loss of the mismatched HLA haplotype. These results suggest that the escape from immunosurveillance by the loss of mismatched HLA alleles may be a crucial mechanism of relapse after HLA-haploidentical HSCT. Accordingly, the status of mismatched HLA on relapsed leukemic cells should be checked before donor lymphocyte infusion.