Graft versus Leukemia effects due to alloreactive NK-cells after HLA mismatched stem cell transplantation in children with refractory leukemia

我们用位点特异性抗体的流式细胞术研究了白血病患者在诊断时和造血干细胞移植(HSCT)后复发患者的白血病细胞上的人类白细胞抗原表达。部分复发患者表现为白血病细胞中的HLA等位基因丢失。单核苷酸多态性阵列分析显示，6号染色体短臂上的获得性单亲二体，导致错配的人类白细胞抗原单倍型完全丧失。我们还发现该患者的原发白血病细胞不被供者的NK细胞杀死，但复发时的白血病细胞在发生了白血病细胞的HLA丢失后被有效地杀死。这些结果提示，人类白细胞抗原失配等位基因丢失而逃避免疫监视可能是人类白细胞抗原半相合HSCT后复发的重要机制。这些发现可能为HSCT后在合适的环境下输注供者NK细胞以防止复发提供理论依据。

We investigated 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. Some relapsed patients demonstrated loss of HLA alleles in leukemic cells at relapse. Single-nucleotide polymorphism array analyses revealed acquired uniparental disomy on the short arm of chromosome 6, resulting in the total loss of the mismatched HLA haplotype. We also found that primary leukemic blasts in this patient were not killed by the donor NK cells, however, leukemic blasts at relapse were efficiently killed after HLA loss of leukemic cells occurred. These results suggested that the escape from immunosurveillance by the loss of mismatched HLA alleles may be a crucial mechanism of relapse after HLA-haploidentical HSCT. These findings may give us the rationale of donor NK cell infusions in suitable setting after HLA haploidentical HSCT to prevent relapse.